Therapeutic polypeptides, nucleic acids encoding same, and methods of use

ABSTRACT

Disclosed herein are nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies that immunospecifically bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the novel polypeptide, polynucleotide, or antibody specific to the polypeptide. Vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same are also included. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. Ser. No. 09/746,491, filed Dec. 20, 2000, and U.S. Ser. No. 10/055,569, filed Oct. 26, 2001, and claims priority to provisional patent applications: U.S. S. No. 60/345,222, filed Jan. 4, 2002; U.S. S. No. 60/348,693, filed Jan. 14, 2002; U.S. S. No. 60/349,182, filed Jan. 16, 2002; U.S. S. No. 60/349,733, filed Jan. 17, 2002; U.S. S. No. 60/350,263, filed Jan. 18, 2002; U.S. S. No. 60/351,977, filed Jan. 24, 2002; U.S. S. No. 60/383,758, filed May 28, 2002; U.S. S. No. 60/385,969, filed Jun. 05, 2002; U.S. S. No. 60/387,834, filed Jun. 11, 2002; U.S. S. No. 60/396,407, filed Jul. 17, 2002; and U.S. S. No. 60/415,115, filed Sep. 30, 2002, each of which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to novel polypeptides, and the nucleic acids encoding them, having properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.

BACKGROUND OF THE INVENTION

[0003] Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins, and signal transducing components located within the cells.

[0004] Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.

[0005] Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.

[0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.

[0007] Antibodies are multichain proteins that bind specifically to a given antigen, and bind poorly, or not at all, to substances deemed not to be cognate antigens. Antibodies are comprised of two short chains termed light chains and two long chains termed heavy chains. These chains are constituted of immunoglobulin domains, of which generally there are two classes: one variable domain per chain, one constant domain in light chains, and three or more constant domains in heavy chains. The antigen-specific portion of the immunoglobulin molecules resides in the variable domains; the variable domains of one light chain and one heavy chain associate with each other to generate the antigen-binding moiety. Antibodies that bind immunospecifically to a cognate or target antigen bind with high affinities. Accordingly, they are useful in assaying specifically for the presence of the antigen in a sample. In addition, they have the potential of inactivating the activity of the antigen.

[0008] Therefore there is a need to assay for the level of a protein effector of interest in a biological sample from such a subject, and to compare this level with that characteristic of a nonpathological condition. In particular, there is a need for such an assay based on the use of an antibody that binds immunospecifically to the antigen. There further is a need to inhibit the activity of the protein effector in cases where a pathological condition arises from elevated or excessive levels of the effector based on the use of an antibody that binds immunospecifically to the effector. Thus, there is a need for the antibody as a product of manufacture. There further is a need for a method of treatment of a pathological condition brought on by an elevated or excessive level of the protein effector of interest based on administering the antibody to the subject.

SUMMARY OF THE INVENTION

[0009] The invention is based in part upon the discovery of isolated polypeptides including amino acid sequences selected from mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52. The novel nucleic acids and polypeptides are referred to herein as NOVX, where X is an identifier for each sequence as shown in Table A below. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.

[0010] The invention also is based in part upon variants of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52. In another embodiment, the invention also comprises variants of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also involves fragments of any of the mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, or any other amino acid sequence selected from this group. The invention also comprises fragments from these groups in which up to 15% of the residues are changed.

[0011] In another embodiment, the invention encompasses polypeptides that are naturally occurring allelic variants of the sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52. These allelic variants include amino acid sequences that are the translations of nucleic acid sequences differing by a single nucleotide from nucleic acid sequences selected from the group consisting of SEQ ID NOS: 2n−1, wherein n is an integer between 1 and 52. The variant polypeptide where any amino acid changed in the chosen sequence is changed to provide a conservative substitution.

[0012] In another embodiment, the invention comprises a pharmaceutical composition involving a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 and a pharmaceutically acceptable carrier. In another embodiment, the invention involves a kit, including, in one or more containers, this pharmaceutical composition.

[0013] In another embodiment, the invention includes the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease being selected from a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 wherein said therapeutic is the polypeptide selected from this group. In another embodiment, the invention comprises a method for determining the presence or amount of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 in a sample, the method involving providing the sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the polypeptide, thereby determining the presence or amount of polypeptide in the sample.

[0014] In another embodiment, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 in a first mammalian subject, the method involving measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in this sample to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0015] In another embodiment, the invention involves a method of identifying an agent that binds to a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, the method including introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. The agent could be a cellular receptor or a downstream effector.

[0016] In another embodiment, the invention involves a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, the method including providing a cell expressing the polypeptide of the invention and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.

[0017] In another embodiment, the invention involves a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, the method including administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of the invention, wherein the test animal recombinantly expresses the polypeptide of the invention; measuring the activity of the polypeptide in the test animal after administering the test compound; and comparing the activity of the protein in the test animal with the activity of the polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the polypeptide of the invention. The recombinant test animal could express a test protein transgene or express the transgene under the control of a promoter at an increased level relative to a wild-type test animal The promoter may or may not b the native gene promoter of the transgene.

[0018] In another embodiment, the invention involves a method for modulating the activity of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, the method including introducing a cell sample expressing the polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.

[0019] In another embodiment, the invention involves a method of treating or preventing a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, the method including administering the polypeptide to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject. The subject could be human.

[0020] In another embodiment, the invention involves a method of treating a pathological state in a mammal, the method including administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 or a biologically active fragment thereof.

[0021] In another embodiment, the invention involves an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52; a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52; a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 or any variant of the polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and the complement of any of the nucleic acid molecules.

[0022] In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the invention involves an isolated nucleic acid molecule including a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

[0023] In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 2n−1, wherein n is an integer between 1 and 52.

[0024] In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of the nucleotide sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52; a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52; and a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.

[0025] In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein the nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or a complement of the nucleotide sequence.

[0026] In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein the nucleic acid molecule has a nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides in the chosen coding sequence are so changed, an isolated second polynucleotide that is a complement of the first polynucleotide, or a fragment of any of them.

[0027] In another embodiment, the invention includes a vector involving the nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52. This vector can have a promoter operably linked to the nucleic acid molecule. This vector can be located within a cell.

[0028] In another embodiment, the invention involves a method for determining the presence or amount of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52 in a sample, the method including providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in the sample. The presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type. The cell type can be cancerous.

[0029] In another embodiment, the invention involves a method for determining the presence of or predisposition for a disease associated with altered levels of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 52 in a first mammalian subject, the method including measuring the amount of the nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0030] The invention further provides an antibody that binds immunospecifically to a NOVX polypeptide. The NOVX antibody may be monoclonal, humanized, or a fully human antibody. Preferably, the antibody has a dissociation constant for the binding of the NOVX polypeptide to the antibody less than 1×10⁻⁹ M. More preferably, the NOVX antibody neutralizes the activity of the NOVX polypeptide.

[0031] In a further aspect, the invention provides for the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, associated with a NOVX polypeptide. Preferably the therapeutic is a NOVX antibody. In yet a further aspect, the invention provides a method of treating or preventing a NOVX-associated disorder, a method of treating a pathological state in a mammal, and a method of treating or preventing a pathology associated with a polypeptide by administering a NOVX antibody to a subject in an amount sufficient to treat or prevent the disorder.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.

[0033] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0034] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides. TABLE A SEQUENCES AND CORRESPONDING SEQ ID NUMBERS SEQ ID NO SEQ ID NO NOVX Internal (nucleic (amino Assignment Identification acid) acid) Homology NOV1a CG108030-01 1 2 Human Sequence NOV1b CG108030-02 3 4 Human Sequence NOV2a CG115907-01 5 6 Trypsin inhibitor precursor NOV2b CG115907-04 7 8 Trypsin inhibitor precursor NOV2c CG115907-03 9 10 Trypsin inhibitor precursor NOV2d CG115907-02 11 12 Trypsin inhibitor precursor NOV3a CG139008-01 13 14 Binding protein NOV3b 233028732 15 16 Binding protein NOV3c CG139008-02 17 18 Binding protein NOV4a CG145877-01 19 20 Hypothetical protein NOV5a CG151161-02 21 22 Myelin and lymphocyte protein NOV5b CG151161-01 23 24 Myelin and lymphocyte protein NOV6a CG155653-01 25 26 Similar to PDZ domain NOV7a CG160093-01 27 28 Leukocyte elastase inhibitor NOV7b CG160093-02 29 30 Leukocyte elastase inhibitor NOV8a CG163133-02 31 32 JM4 protein NOV8b CG163133-01 33 34 JM4 protein NOV9a CG165528-01 35 36 Neurexin 1-alpha precursor NOV9b CG165528-02 37 38 Neurexin 1-alpha precursor NOV10a CG165666-01 39 40 Similar to TPR-containing protein NOV11a CG165676-01 41 42 Integrin, alpha 2 NOV12a CG165719-04 43 44 Neuronal membrane protein M6-B NOV12b CG165719-02 45 46 Neuronal membrane protein M6-B NOV12c CG165719-03 47 48 Neuronal membrane protein M6-B NOV12d CG165719-01 49 50 Neuronal membrane protein M6-B NOV12e CG165719-05 51 52 Neuronal membrane protein M6-B NOV13a CG167488-02 53 54 Human protein NOV13b CG167488-01 55 56 Human protein NOV14a CG173318-01 57 58 Human protein NOV15a CG50970-06 59 60 cerebroglycan NOV15b CG50970-01 61 62 cerebroglycan NOV15d 274054257 63 64 cerebroglycan NOV15e CG50970-03 65 66 cerebroglycan NOV15f 237922026 67 68 cerebroglycan NOV15g 237922511 69 70 cerebroglycan NOV15h 315490136 71 72 cerebroglycan NOV15i CG50970-02 73 74 cerebroglycan NOV15j CG50970-04 75 76 cerebroglycan NOV15k CG50970-05 77 78 cerebroglycan NOV15l CG50970-07 79 80 cerebroglycan NOV16a CG54443-03 81 82 Hypothetical Protein NOV16b CG54443-07 83 84 Hypothetical Protein NOV16c CG54443-01 85 86 Hypothetical Protein NOV16d CG54443-02 87 88 Hypothetical Protein NOV16e CG54443-04 89 90 Hypothetical Protein NOV16f CG54443-05 91 92 Hypothetical Protein NOV16g CG54443-06 93 94 Hypothetical Protein NOV17a CG58495-01 95 96 pulmonary surfactant protein NOV17b CG58495-03 97 98 pulmonary surfactant protein NOV17c CG58495-02 99 100 pulmonary surfactant protein NOV18a CG97482-01 101 102 S-100 protein, beta chain NOV18b CG97482-02 103 104 S-100 protein, beta chain

[0035] Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.

[0036] Pathologies, diseases, disorders and conditions and the like that are associated with NOVX sequences include, but are not limited to: e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), vascular calcification, fibrosis, atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, osteoarthritis, rheumatoid arthritis, osteochondrodysplasia, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, glomerulonephritis, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, psoriasis, skin disorders, graft versus host disease, AIDS, bronchial asthma, lupus, Crohn's disease; inflammatory bowel disease, ulcerative colitis, multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, schizophrenia, depression, asthma, emphysema, allergies, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo).

[0037] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.

[0038] Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.

[0039] The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.

[0040] The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g. detection of a variety of cancers.

[0041] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0042] NOVX Clones

[0043] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.

[0044] The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.

[0045] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.

[0046] In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).

[0047] In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 52; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 52, or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement of any of said nucleic acid molecules.

[0048] In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 52; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 52, is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 52; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 52, is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.

[0049] NOVX Nucleic Acids and Polypeptides

[0050] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.

[0051] A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.

[0052] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

[0053] The term “isolated” nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.

[0054] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL 2^(nd) Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y., 1993.)

[0055] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer. As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0056] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, thereby forming a stable duplex.

[0057] As used herein, the term “complementary” refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term “binding” means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.

[0058] A “fragment” provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.

[0059] A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 5′ direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3′ direction of the disclosed sequence.

[0060] A “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g. they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.

[0061] Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y., 1993, and below.

[0062] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0063] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.

[0064] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52; or of a naturally occurring mutant of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52. Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe has a detectable label attached, e.g. the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.

[0065] “A polypeptide having a biologically-active portion of a NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.

[0066] NOVX Nucleic Acid and Polypeptide Variants

[0067] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 52.

[0068] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.

[0069] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.

[0070] Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.

[0071] Homologs (i.e., nucleic acids encoding NOVX proteins derived from species other than human) or other related sequences (e.g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning. As used herein, the phrase “stringent hybridization conditions” refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60° C. for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.

[0072] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).

[0073] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5× Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.

[0074] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.

[0075] Conservative Mutations

[0076] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 52. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an “essential” amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

[0077] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 52. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 52; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 52; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 52; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 52; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 52.

[0078] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 52, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0079] Mutations can be introduced any one of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0080] The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved “strong” residues or fully conserved “weak” residues. The “strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the “weak” group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.

[0081] In one embodiment, a mutant NOVX protein can be assayed for (i) the ability to form protein:protein interactions with other NOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant NOVX protein and a NOVX ligand; or (iii) the ability of a mutant NOVX protein to bind to an intracellular target protein or biologically-active portion thereof; (e.g. avidin proteins). In yet another embodiment, a mutant NOVX protein can be assayed for the ability to regulate a specific biological function (e.g., regulation of insulin release).

[0082] Interfering RNA

[0083] In one aspect of the invention, NOVX gene expression can be attenuated by RNA interference. One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5′ untranslated (UT) region, the ORF, or the 3′ UT region. See, e.g., PCT applications WO00/44895, WO99/32619, WO01/75164, WO01/92513, WO 01/29058, WO01/89304, WO02/16620, and WO02/29858, each incorporated by reference herein in their entirety. Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene. Nonlimiting examples of upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway.

[0084] According to the methods of the present invention, NOVX gene expression is silenced using short interfering RNA. A NOVX polynucleotide according to the invention includes a siRNA polynucleotide. Such a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence. See, e.g., Tuschl, Zamore, Lehmann, Bartel and Sharp (1999), Genes & Dev. 13: 3191-3197, incorporated herein by reference in its entirety. When synthesized, a typical 0.2 micromolar-scale RNA synthesis provides about 1 milligram of siRNA, which is sufficient for 1000 transfection experiments using a 24-well tissue culture plate format.

[0085] The most efficient silencing is generally observed with siRNA duplexes composed of a 21-nt sense strand and a 21-nt anti sense strand, paired in a manner to have a 2-nt 3′ overhang. The sequence of the 2-nt 3′ overhang makes an additional small contribution to the specificity of siRNA target recognition. The contribution to specificity is localized to the unpaired nucleotide adjacent to the first paired bases. In one embodiment, the nucleotides in the 3′ overhang are ribonucleotides. In an alternative embodiment, the nucleotides in the 3′ overhang are deoxyribonucleotides. Using 2′-deoxyribonucleotides in the 3′ overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.

[0086] A contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands. An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3′ of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5′ of the cloned DNA). The sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene. Alternatively, two constructs can be utilized to create the sense and anti-sense strands of a siRNA construct. Finally, cloned DNA can encode a construct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes. In an example of this embodiment, a hairpin RNAi product is homologous to all or a portion of the target gene. In another example, a hairpin RNAi product is a siRNA. The regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.

[0087] In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA H1. One example of a vector system is the GeneSuppressor™ RNA Interference kit (commercially available from Imgenex). The U6 and H1 promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for H1 promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3′ UU overhang in the expressed siRNA, which is similar to the 3′ overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21-nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.

[0088] A siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.

[0089] In general, siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER. DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex. In vitro studies in Drosophila suggest that the siRNAs/protein complex (siRNP) is then transferred to a second enzyme complex, called an RNA-induced silencing complex (RISC), which contains an endoribonuclease that is distinct from DICER. RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.

[0090] A NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 to 100 nt downstream of the start codon. Alternatively, 5′ or 3′ UTRs and regions nearby the start codon can be used but are generally avoided, as these may be richer in regulatory protein binding sites. UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex. An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6877-88. Hence, consideration should be taken to accommodate SNPs, polymorphisms, allelic variants or species-specific variations when targeting a desired gene.

[0091] In one embodiment, a complete NOVX siRNA experiment includes the proper negative control. A negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.

[0092] Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect. In addition, expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide. Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility.

[0093] A targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT). A desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21). The sequence of the NOVX sense siRNA corresponds to (N19)TT or N21, respectively. In the latter case, conversion of the 3′ end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3′ overhangs. Symmetric 3′ overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes & Dev. 15: 188-200, incorporated by reference herein in its entirely. The modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.

[0094] Alternatively, if the NOVX target mRNA does not contain a suitable AA(N21) sequence, one may search for the sequence NA(N21). Further, the sequence of the sense strand and antisense strand may still be synthesized as 5′ (N19)TT, as it is believed that the sequence of the 3′-most nucleotide of the antisense siRNA does not contribute to specificity. Unlike antisense or ribozyme technology, the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et al. (2001) J. Cell Science 114: 4557-4565, incorporated by reference in its entirety.

[0095] Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECTAMINE Reagent (commercially available from Invitrogen). An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes. In a specific embodiment, for one well of a 24-well plate, approximately 0.84 μg of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence. The choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type. The efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells. The time and the manner of formation of siRNA-liposome complexes (e.g. inversion versus vortexing) are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing. The efficiency of transfection needs to be carefully examined for each new cell line to be used. Preferred cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human. Where used for therapeutic treatment, the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention.

[0096] For a control experiment, transfection of 0.84 μg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 μg antisense siRNA has a weak silencing effect when compared to 0.84 μg of duplex siRNAs. Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes. To control for transfection efficiency, targeting of common proteins is typically performed, for example targeting of lamin A/C or transfection of a CMV-driven EGFP-expression plasmid (e.g. commercially available from Clontech). In the above example, a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression. Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.

[0097] Depending on the abundance and the half life (or turnover) of the targeted NOVX polynucleotide in a cell, a knock-down phenotype may become apparent after 1 to 3 days, or even later. In cases where no NOVX knock-down phenotype is observed, depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If the NOVX polynucleotide is still abundant after 3 days, cells need to be split and transferred to a fresh 24-well plate for re-transfection. If no knock-down of the targeted protein is observed, it may be desirable to analyze whether the target mRNA (NOVX or a NOVX upstream or downstream gene) was effectively destroyed by the transfected siRNA duplex. Two days after transfection, total RNA is prepared, reverse transcribed using a target-specific primer, and PCR-amplified with a primer pair covering at least one exon-exon junction in order to control for amplification of pre-mRNAs. RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell. Multiple transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.

[0098] An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or aberrant NOVX expression or activity. The NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above. The NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above. A NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues. The present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi construct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation. A specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.

[0099] Where the NOVX gene function is not correlated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA's to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX⁻) phenotype in the treated subject sample. The NOVX⁻ phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.

[0100] In specific embodiments, a NOVX siRNA is used in therapy. Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.

[0101] Production of RNAs

[0102] Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors. In the initial experiments, the sense and antisense RNA are about 500 bases in length each. The produced ssRNA and asRNA (0.5 μM) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C. for 1 min then cooled and annealed at room temperature for 12 to 16 h. The RNAs are precipitated and resuspended in lysis buffer (below). To monitor annealing, RNAs are electrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).

[0103] Lysate Preparation

[0104] Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer's directions. dsRNA is incubated in the lysate at 30° C. for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double stranded RNA and mRNA is about 200:1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.

[0105] In a parallel experiment made with the same conditions, the double stranded RNA is internally radiolabeled with a ³²P-ATP. Reactions are stopped by the addition of 2× proteinase K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined.

[0106] The band of double stranded RNA, about 21-23 bps, is eluded. The efficacy of these 21-23 mers for suppressing NOVX transcription is assayed in vitro using the same rabbit reticulocyte assay described above using 50 nanomolar of double stranded 21-23 mer for each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techniques.

[0107] RNA Preparation

[0108] 21 nt RNAs, based on the sequence determined above, are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, & Tuschl, Genes & Dev. 15, 188-200 (2001)), followed by Sep-Pak C18 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)).

[0109] These RNAs (20 μM) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 9⁰° C. followed by 1 h at 37° C.

[0110] Cell Culture

[0111] A cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1−3×105 cells/ml) and transferred to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3′ ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used. An efficient concentration for suppression in vitro in mammalian culture is between 25 nM to 100 nM final concentration. This indicates that siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.

[0112] The above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression. In vivo suppression may be performed using the same siRNA using well known in vivo transfection or gene therapy transfection techniques.

[0113] Antisense Nucleic Acids

[0114] Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 52, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, are additionally provided.

[0115] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a NOVX protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding the NOVX protein. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).

[0116] Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used). Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N-6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

[0117] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.

[0118] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual 1-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl. Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.

[0119] Ribozymes and PNA Moieties

[0120] Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.

[0121] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988. Nature 334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2n−1, wherein n is an integer between 1 and 52). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993) Science 261:1411-1418.

[0122] Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 1991. Anticancer Drug Des. 6: 569-84; Helene, et al. 1992. Ann. N.Y. Acad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15.

[0123] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675.

[0124] PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S1 nucleases (See, Hyrup, et al., 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O'Keefe, et al., 1996. supra).

[0125] In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996. Nucl Acids Res 24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, e.g., Mag, et al., 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g. Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975. Bioorg. Med. Chem. Lett. 5:1119-11124.

[0126] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al., 1987. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.

[0127] NOVX Polypeptides

[0128] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 52. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 52, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0129] In general, a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.

[0130] One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

[0131] An “isolated” or “purified” polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language “substantially free of cellular material” includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced. In one embodiment, the language “substantially free of cellular material” includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also referred to herein as a “contaminating protein”), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins. When the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.

[0132] The language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.

[0133] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 52) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.

[0134] Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.

[0135] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 52. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 52, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 52, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 52, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 52.

[0136] Determining Homology Between Two or More Sequences

[0137] To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid “homology” is equivalent to amino acid or nucleic acid “identity”).

[0138] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. J Mol Biol 48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52.

[0139] The term “sequence identity” refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term “percentage of sequence identity” is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term “substantial identity” as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.

[0140] Chimeric and Fusion Proteins

[0141] The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX “chimeric protein” or “^(t)fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 52, whereas a “non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within a NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein. Within the fusion protein, the term “operatively-linked” is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.

[0142] In one embodiment, the fusion protein is a GST-NOVX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant NOVX polypeptides.

[0143] In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.

[0144] In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g. promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand. A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.

[0145] NOVX Agonists and Antagonists

[0146] The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists. Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein). An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein. An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.

[0147] Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g., truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity. In one embodiment, a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein. There are a variety of methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3; Itakura, et al., 1984. Annu. Rev. Biochem. 53: 323; Itakura, et al., 1984. Science 198: 1056; Ike, et al., 1983. Nucl. Acids Res. 11: 477.

[0148] Polypeptide Libraries

[0149] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.

[0150] Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of NOVX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e.g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89: 7811-7815; Delgrave, et al., 1993. Protein Engineering 6:327-331.

[0151] Anti-NOVX Antibodies

[0152] Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, F_(ab), F_(ab′) and F_((ab′)2) fragments, and an F_(ab) expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG₁, IgG₂, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.

[0153] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 52, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope. Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues. Preferred epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.

[0154] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol. Biol. 157: 105-142, each incorporated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0155] The term “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (K_(D)) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.

[0156] A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.

[0157] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.

[0158] Polyclonal Antibodies

[0159] For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).

[0160] The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8-(Apr. 17, 2000), pp. 25-28).

[0161] Monoclonal Antibodies

[0162] The term “monoclonal antibody” (MAb) or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.

[0163] Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro.

[0164] The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly mycloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (“HAT medium”), which substances prevent the growth of HGPRT-deficient cells.

[0165] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

[0166] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.

[0167] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding, 1986). Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.

[0168] The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

[0169] The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.

[0170] Humanized Antibodies

[0171] The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′)₂ or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Pat. No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fe), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)).

[0172] Human Antibodies

[0173] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).

[0174] In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al, (Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).

[0175] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.

[0176] An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Pat. No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.

[0177] A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Pat. No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.

[0178] In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a correlative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT publication WO 99/53049.

[0179] F_(ab) Fragments and Single Chain Antibodies

[0180] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of F_(ab) expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal F_(ab) fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F_((ab′)2) fragment produced by pepsin digestion of an antibody molecule; (ii) an F_(ab) fragment generated by reducing the disulfide bridges of an F_((ab′)2) fragment; (iii) an F_(ab) fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F_(v) fragments.

[0181] Bispecific Antibodies

[0182] Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.

[0183] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0184] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).

[0185] According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.

[0186] Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab′)₂ bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′)₂ fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives is then reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.

[0187] Additionally, Fab′ fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab′)₂ molecule. Each Fab′ fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.

[0188] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5): 1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (V_(H)) connected to a light-chain variable domain (V_(L)) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V_(H) and V_(L) domains of one fragment are forced to pair with the complementary V_(L) and V_(H) domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).

[0189] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0190] Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fe receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).

[0191] Heteroconjugate Antibodies

[0192] Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies, for example, target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980), and for treatment of HIV infection (WO 91/00360; WO 92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Pat. No. 4,676,980.

[0193] Effector Function Engineering

[0194] It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).

[0195] Immunoconjugates

[0196] The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).

[0197] Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include ²¹²Bi, ¹³¹I, ¹³¹In, ⁹⁰Y, and ¹⁸⁶Re.

[0198] Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science, 238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.

[0199] In another embodiment, the antibody can be conjugated to a “receptor” (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a “ligand” (e.g., avidin) that is in turn conjugated to a cytotoxic agent.

[0200] Immunoliposomes

[0201] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.

[0202] Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst., 81(19): 1484 (1989).

[0203] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0204] In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0205] Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”).

[0206] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵I, ¹³¹I, ³⁵S or ³H.

[0207] Antibody Therapeutics

[0208] Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.

[0209] Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.

[0210] A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.

[0211] Pharmaceutical Compositions of Antibodies

[0212] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York. If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.

[0213] The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.

[0214] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0215] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.

[0216] ELISA Assay

[0217] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., F_(ab) or F_((ab)2)) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Theory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0218] NOVX Recombinant Expression Vectors and Host Cells

[0219] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.

[0220] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).

[0221] The term “regulatory sequence” is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).

[0222] The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

[0223] Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

[0224] Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).

[0225] One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (see, e.g., Wada, et al., 1992. Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.

[0226] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSec 1 (Baldari, et al., 1987. EMBO J. 6: 229-234), pMFa (Kuijan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

[0227] Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al., 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31-39).

[0228] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987. EMBO J. 6: 187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.

[0229] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Baneiji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).

[0230] The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub, et al., “Antisense RNA as a molecular tool for genetic analysis,” Reviews-Trends in Genetics, Vol. 1(1) 1986.

[0231] Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein. A host cell can be any prokaryotic or eukaryotic cell. For example, NOVX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

[0232] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.

[0233] For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Various selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).

[0234] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.

[0235] Transgenic NOVX Animals

[0236] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and/or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.

[0237] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes.

[0238] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of any one of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector).

[0239] Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein). In the homologous recombination vector, the altered portion of the NOVX gene is flanked at its 5′- and 3′-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell. The additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5′- and 3′-termini) are included in the vector. See, e.g., Thomas, et al., 1987. Cell 51: 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al., 1992. Cell 69: 915.

[0240] The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 1987. In: TERATOCARCINOMAS AND EMBRYONIC STEM CELLS: A PRACTICAL APPROACH, Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991. Curr. Opin. Biotechnol. 2: 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.

[0241] In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, See, e.g., Lakso, et al., 1992. Proc. Natl. Acad. Sci. USA 89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al., 1991. Science 251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.

[0242] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter G₀ phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.

[0243] Pharmaceutical Compositions

[0244] The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVX antibodies (also referred to herein as “active compounds”) of the invention, and derivatives, fragments, analogs and homologs thereof, can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein, “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.

[0245] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0246] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifuingal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0247] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0248] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0249] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.

[0250] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0251] The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

[0252] In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomnes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.

[0253] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.

[0254] The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Pat. No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al., 1994. Proc. Natl. Acad. Sci. USA 91: 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system.

[0255] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0256] Screening and Detection Methods

[0257] The isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or aberrant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease (possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absorption of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.

[0258] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0259] Screening Assays

[0260] The invention provides a method (also referred to herein as a “screening assay”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity. The invention also includes compounds identified in the screening assays described herein.

[0261] In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 1997. Anticancer Drug Design 12: 145.

[0262] A “small molecule” as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.

[0263] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993. Proc. Natl. Acad. Sci. U.S.A. 90: 6909; Erb, et al., 1994. Proc. Natl. Acad. Sci. U.S.A. 91: 11422; Zuckermann, et al., 1994. J. Med. Chem. 37: 2678; Cho, et al., 1993. Science 261: 1303; Carrell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33: 2059; Carell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33: 2061; and Gallop, et al., 1994. J. Med. Chem. 37: 1233.

[0264] Libraries of compounds may be presented in solution (e.g., Houghten, 1992. Biotechniques 13: 412-421), or on beads (Lam, 1991. Nature 354: 82-84), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992. Proc. Natl. Acad. Sci. USA 89: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al., 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Pat. No. 5,233,409.).

[0265] In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with ¹²⁵I, ³⁵S, ¹⁴C, or ³H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.

[0266] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule. As used herein, a “target molecule” is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g. a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.

[0267] Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e. intracellular Ca²⁺, diacylglycerol, IP₃, etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.

[0268] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.

[0269] In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g. stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.

[0270] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.

[0271] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesite, Isotridecypoly(ethylene glycol ether)_(n), N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).

[0272] In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NOVX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.

[0273] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.

[0274] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.

[0275] In yet another aspect of the invention, the NOVX proteins can be used as “bait proteins” in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al., 1993. Cell 72: 223-232; Madura, et al., 1993. J. Biol. Chem. 268: 12046-12054; Bartel, et al., 1993. Biotechniques 14: 920-924; Iwabuchi, et al., 1993. Oncogene 8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.

[0276] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.

[0277] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0278] Detection Assays

[0279] Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.

[0280] Chromosome Mapping

[0281] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping of the NOVX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.

[0282] Briefly, NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis of the NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the NOVX sequences will yield an amplified fragment.

[0283] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D'Eustachio, et al., 1983. Science 220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.

[0284] PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.

[0285] Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al., HUMAN CHROMOSOMES: A MANUAL OF BASIC TECHNIQUES (Pergamon Press, New York 1988).

[0286] Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.

[0287] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al., 1987. Nature, 325: 783-787.

[0288] Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymorphisms.

[0289] Tissue Typing

[0290] The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP (“restriction fragment length polymorphisms,” described in U.S. Pat. No. 5,272,057).

[0291] Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5′- and 3′-termini of the sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.

[0292] Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymorphisms (SNPs), which include restriction fragment length polymorphisms (RFLPs).

[0293] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0294] Predictive Medicine

[0295] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.

[0296] Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as “pharmacogenomics”). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)

[0297] Yet another aspect of the invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials.

[0298] These and other agents are described in further detail in the following sections.

[0299] Diagnostic Assays

[0300] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n−1, wherein n is an integer between 1 and 52, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.

[0301] An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab′)₂) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0302] In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.

[0303] In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.

[0304] The invention also encompasses kits for detecting the presence of NOVX in a biological sample. For example, the kit can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid.

[0305] Prognostic Assays

[0306] The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. For example, the assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with aberrant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. As used herein, a “test sample” refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.

[0307] Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder. Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e.g., wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant NOVX expression or activity).

[0308] The methods of the invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of: (i) a deletion of one or more nucleotides from a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing pattern of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

[0309] In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al., 1988. Science 241: 1077-1080; and Nakazawa, et al., 1994. Proc. Natl. Acad. Sci. USA 91: 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al., 1995. Nucl. Acids Res. 23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification of the NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.

[0310] Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al., 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

[0311] In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.

[0312] In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al., 1996. Human Mutation 7: 244-255; Kozal, et al., 1996. Nat. Med. 2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al., supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

[0313] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence of the sample NOVX with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g., Naeve, et al., 1995. Biotechniques 19: 448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen, et al., 1996. Adv. Chromatography 36: 127-162; and Griffin, et al., 1993. Appl. Biochem. Biotechnol. 38: 147-159).

[0314] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985. Science 230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S₁ nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85: 4397; Saleeba, et al., 1992. Methods Enzymol. 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.

[0315] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al., 1994. Carcinogenesis 15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g., a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Pat. No. 5,459,039.

[0316] In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in NOVX genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e.g., Orita, et al., 1989. Proc. Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285: 125-144; Hayashi, 1992. Genet. Anal. Tech. Appl. 9: 73-79. Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g., Keen, et al., 1991. Trends Genet. 7: 5. In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE). See, e.g., Myers, et al., 1985. Nature 313: 495. When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987. Biophys. Chem. 265: 12753.

[0317] Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g., Saiki, et al., 1986. Nature 324: 163; Saiki, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.

[0318] Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al., 1989. Nucl. Acids Res. 17: 2437-2448) or at the extreme 3′-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech. 11: 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. See, e.g., Gasparini, et al., 1992. Mol. Cell Probes 6: 1. It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e.g., Barany, 1991. Proc. Natl. Acad. Sci. USA 88: 189. In such cases, ligation will occur only if there is a perfect match at the 3′-terminus of the 5′ sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.

[0319] The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.

[0320] Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.

[0321] Pharmacogenomics

[0322] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0323] In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) of the individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e.g., drugs) for prophylactic or therapeutic treatments based on a consideration of the individual's genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual.

[0324] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol., 23: 983-985; Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymorphisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

[0325] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C 19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C 19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.

[0326] Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.

[0327] Monitoring of Effects During Clinical Trials

[0328] Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX (e.g., the ability to modulate aberrant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase NOVX gene expression, protein levels, or upregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting decreased NOVX gene expression, protein levels, or downregulated NOVX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease NOVX gene expression, protein levels, or downregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting increased NOVX gene expression, protein levels, or upregulated NOVX activity. In such clinical trials, the expression or activity of NOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a “read out” or markers of the immune responsiveness of a particular cell.

[0329] By way of example, and not of limitation, genes, including NOVX, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) that modulates NOVX activity (e.g., identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (i.e., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods as described herein, or by measuring the levels of activity of NOVX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment of the individual with the agent.

[0330] In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.

[0331] Methods of Treatment

[0332] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0333] These methods of treatment will be discussed more fully, below.

[0334] Diseases and Disorders

[0335] Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i.e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; (ii) antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are “dysfunctional” (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to “knockout” endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989. Science 244: 1288-1292); or (v) modulators (i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.

[0336] Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i.e., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability. Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like).

[0337] Prophylactic Methods

[0338] In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.

[0339] Therapeutic Methods

[0340] Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.

[0341] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).

[0342] Determination of the Biological Effect of the Therapeutic

[0343] In various embodiments of the invention, suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment of the affected tissue.

[0344] In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.

[0345] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0346] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0347] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.

[0348] Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein of the invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods.

[0349] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES Example A Polynucleotide and Polypeptide Sequences, and Homology Data Example 1

[0350] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A. TABLE 1A NOV1 Sequence Analysis SEQ ID NO: 1               2566 bp NOV1a, GGNCACGAGCGGCCCTCCACTCCCTGACTGTCGTGTTTGTCTCGCTCTGTGCTGAGGGCTGATG CG108030-01 DNA Sequence CTGAGGACCTCCTTGACTCCTTCCTTAGCAACATTCTACAGGACTGCAGGCACCACCTGTGTGA ACCGGACATGAAACTGGTGTGGCCTAGTGCCAAGCTGTTGCAGGCAGCTGCAGGTGCATCTGCC CGGGCCTGTGACTCTGTCACCAGCAAGTACTGCCTTTACTGCTGGAACAGTTCCACAAGCACAG TCAGAGCAGCCAGCGGCGGACAATCCTTGAA ATGCTCCTGGGTTTCTTGAAGCTGCAGCAGAAA TGGAGCTATGAAGACAAAGATCAAAGGCCTCTGAATGGCTTCAAGGACCAGCTGTGCTCACTGG TATTCATGGCTCTAACAGACCCCAGCACCCAGCTTCAGCTTGTTGGCATCCGTACACTGACAGT CTTGGGTGCCCAGCCAGATCTCCTATCTTATGAGGACTTGGAGCTGGCAGTGGGTCACCTGTAC AGACTGAGCTTCCTGAAGGAGGATTCCCAGAGTTGCAGGGTGGCAGCACTGGAAGCATCAGGAA CCCTGGCTGCTCTCTACCCTGTGGCCTTCAGCAGCCACCTCGTACCCAAGCTCGCTGAGGAGCT GCGTGTAGGGGAGTCAAATTTGACTAACGGAGATGAGCCCACCCAATGCTCCCGGCATCTGTGC TGTCTGCAAGCCTTGTCAGCTGTATCAACACATCCCAGCATCGTCAAGGAGACACTGCCTCTGC TGTCTGTCAGAGCCTCAGACAGATGGCAGAAAAATGTCAGCAGGACCCTGAGAGTTGCTGGTAT TTCCACCAGACAGCTATACCTTGCCTGCTTGCCTTGGCTGTGCAGGCCTCTATGCCAGAGAAGG AGCCCTCAGTTCTGAGAAAAGTACTATTGGAGGATGAGGTGTTGGCTGCCATGGTGTCTGTCAT TGGCACTGCTACAACCCACCTGAGCCCTGAGTTAGCTGCCCAGAGTGTGACACACATTGTGCCC CTCTTCTTGGATGGCAACGTGTCCTTTCTGCCTGAAAACAGCTTCCCGAGCAGATTCCAGCCAT TCCAGGATGGCTCCTCAGGGCAGAGGCGGCTGATTGCACTGCTTATGGCCTTTGTCTGCTCCCT GCCTCGAAATGTGGAAATCCCTCAGCTGAACCAACTCATGCGGGAGCTTTTGGAACTGAGCTGC TGCCACAGCTGCCCCTTTTCTTCCACCGCTGCTGCCAAGTGCTTTGCAGGACTCCTCAACAAGC ACCCTGCAGGGCAGCAGCTGGATGAATTCCTACAGCTAGCTGTGGACAAAGTGGAGGCTGGCCT GGCTCTGGGCCCTGTCGTAGTCAGGCCTTCACTCTTCTTCTCTGGGTAA CAAAGGCCCTAGTGC TCAGATACCATCCTCTCAGCTCCTGCCTTACAGCCCGGCTCATGGGCCTCCTGAGTGACCCAGA ATTAGGTCCAGCAGCAGCTGGATGGCTTCTCTCTGCTCATGTCTGACTGACTGATGTGCTGACT CGTGCTGGCCATGCCGAAGTGCGGATCATGTTCCGCCAGCGGTTCTTCACAGATAATGTGCCTG CTTTGGTCCAGGGCTTCCATGCTGCTCCCCAAGATGTGAAGCCAAACTACTTGAAGGGTCTTTC TCATGTACTTAACAGGCTGCCCAAGCCTGACTCTTGCCAGAGCTGCCCACGCTTCTTTCCTTGC TGCTGGAGGCCCTGTCCTGCCCTGACTGTGTGGTGCAGCTCTCCACCCTCAGCTGCCTTCAGCC TCTTCTACTGGAAGCACCCCAAGTCATGAGTCTTCACGTGGACACCCTCGTCACCAAGTTTCTG AACCTCAGCTCTAGCCCTTCCATGGCTGTCCGGATCGCCGCACTGCAGTGCATGCATGCTCTCA CTCGCCTGCCCACCCCTGTGCTGCTGCCGTACAAACCACAGGTGATTCGGGCCTTAGCCAAACC CCTGGATGACAAGAAGAGACTGGTGCGCAAGGAAGCAGTGTCAGCCAGAGGGGAGTGGTTTCTG TTGGGGAGCCCTGGCAGCTGAGCCCTCAGTCCTGGCCTAGACTGTTCTGACAATCTAACCTGGG ATTACTAACTGTTGAGCCATCTTCCCCAAAGCAGGGAAACCACTGGTCTCTGACTGCCTTTCCC ACAGACACAGCACAAATGCTAGGCCTCTGTTGCATGGCTGTACAAAGAACATAAGAGTCCATAT TTCTAGTGGATTTGTAAAATAAGTGTGTGTGAGACACTTGCGTTTGAAGAAAGATCTAGGGTCC TGGGTCTCTTGCATTTATATGTCAGAAAAGGGGCGATATGCTGCTGAGGGGTGAGTGCATATGA GTGTGGCCCTGAGGACCAGGGCTGGCAGATGTTGTCTACCTGCTGAAGAATAAAGATTTCTTTT GGTAAAAAAAAAAAAAAAGGGCGGCCGCTCTAGAGGATCCCTCGAGGGGCGCAAGCTTACGCGA NCANGC ORF Start: ATG at 288                      ORF Stop: TAA at 1455 SEQ ID NO: 2                389 aa         MW at 42642.8 kD NOV1a, MLLGFLKLQQKWSYEDKDQRPLNGFKDQLCSLVFMALTDPSTQLQLVGIRTLTVLGAQPDLLSY CG108030-01 Protein Sequence EDLELAVGHLYRLSFLKEDSQSCRVAALEASGTLAALYPVAFSSHLVPKLAEELRVGESNLTNG DEPTQCSRHLCCLQALSAVSTHPSIVKETLPLLLQHLWQVNRGNMVAQSSDVIAVCQSLRQMAE KCQQDPESCWYFHQTAIPCLLALAVQASMPEKEPSVLRKVLLEDEVLAAMVSVIGTATTHLSPE LAAQSVTHIVPLFLDGNVSFLPENSFPSRFQPFQDGSSGQRRLIALLMAFVCSLPRNVEIPQLN QLMRELLELSCCHSCPFSSTAAAKCFAGLLNKHPAGQQLDEFLQLAVDKVEAGLALGPVVVRPS LFFSG SEQ ID NO: 3               3319 bp NOV1b, TCGCGTT ATGGCCGCTGCCGCGGCTGTGGAGGCGGCGGCGCCTATGGGTGCCCTATGGGGCCTC CG108030-02 DNA Sequence GTGCACGACTTCGTCGTGGGTCAGCAAGAGGGCCCCGCTGACCAGGTGGCTGCAGATGTGAAAT CTGGCAACTATACAGTGTTACAAGTTGTGGAAGCCCTTGGGTCCTCTCTAGAGAATCCAGAACC CCGAACTCGGGCACGAGGAATCCAGCTTTTGTCACAGGTGCTACTCCACTGTCACACCTTGCTC CTGGAGAAGGAAGTGGTACACCTGATACTGTTCTATGAGAACCGGCTGAAGGACCATCATCTTG TGATCCCATCTGTCCTGCAGGGTTTGAAGGCACTTAGCCTGTGTGTGGCCCTGCCCCCAGGGCT GGCTGTTTCTGTGCTTAAAGCCATCTTCCAGGAAGTGCATGTACAGTCCCTGCCACAGGTGGAC CGACACACAGTCTACAATATCATCACCAATTTTATGCGAACCCGGGAAGAAGAGCTAAAGAGCC TAGGAGCTGACTTCACCTTTGGCTTCATCCAGGTGATGGATGGGGAAAAGGATCCCCGTAATCT TCTGGTGGCCTTCCGCATCGTCCATGACCTCATCTCCAGGGACTATAGCCTGGGACCCTTTGTG GAGGAGTTGTTTGAAGTGACATCCTGTTATTTCCCTATCGATTTTACCCCTCCACCTAATGATC CCCATGGTATCCAGAGAGAAGACCTCATCCTGAGTCTTCGCGCTGTGCTGGCTTCTACACCACG ATTTGCTGAGTTTCTGCTGCCCCTGTTGATTGAGAAAGTGGATTCTGAGGTTCTGAGTGCCAAG TTGGATTCTCTACAGACTCTGAATGCTTGCTGTGCTGTGTATGGACAGAAGGAACTGAAGGACT TCCTCCCCAGCCTTTGGGCTTCTATCCGCAGAGAGGTGTTCCAGACGGCAAGTGAGCGGGTGGA GGCAGAGGGCCTGGCGGCCCTCCACTCCCTGACTGCGTGTTTGTCTCCCTCTGTGCTGAGGGCT GATGCTGAGGACCTCCTTGACTCCTTCCTTAGCAACATTCTACAGGACTGCAGGCACCACCTGT GTGAACCGGACATGAAACTGGTGTGGCCTAGTGCAAGCTGTTGCAGGCAGCTGCAGGTGCATCT GCCCGGGCCTGTGACTCTGTCACCAGCAATGTACTGCCTTTACTGCTGGAACAGTTCCACAAGC ACAGTCAGAGCAGCCAGCGGCGGGACAATCCTTGAAATGCTCCTGGGTTTCTTGAAGCTGCAGC AGAAATGGAGCTATGAAGACAAAGATCAAAGGCCTCTGAATGGCTTCAAGGACCAGCTGTGCTC ACTGGTATTCATGGCTCTAACAGACCCCAGCACCCAGCTTCAGCTTGTTGGCATCCGTACACTG ACAGTCTTGGGTGCCCAGCCAGATCTCCTATCTTATGAGGACTTGGAGCTGGCAGTGGGTCACC TGTACAGACTGAGCTTCCTGAAGGAGGATTCCCAGAGTTGCAGGGTGGCAGCACTGGAAGCATC AGGAACCCTGGCTGCTCTCTACCCTGTGGCCTTCAGCAGCCACCTCGTACCCAAGCTCGCTGAG GAGCTGCGTGTAGGGGAGTCAAATTTGACTAACGGAGATGAGCCCACCCAATGCTCCCGGCATC TGTGCTGTCTGCAAGCCTTGTCAGCTGTATCAACACATCCCAGCATCGTCAAGGAGACACTGCC TCTGCTGCTGCAGCATCTCTGGCAAGTGAACAGAGGGAATATGGTTGCACAATCCAGTGACGTT ATTGCTGTCTGTCAGAGCCTCAGACAGATGGCAGAAAAATGTCAGCAGGACCCTGAGAGTTGCT GGTATTTCCACCAGACAGCTATACCTTGCCTGCTTGCCTTGGCTGTGCAGGCCTCTATGCCAGA GAAGGAGCCCTCAGTTCTGAGAAAAGTACTATTGGAGGATGAGGTGTTGGCTGCCATGGTGTCT GTCATTGGCACTGCTACAACCCACCTGAGCCCTGAGTTAGCTGCCCAGAGTGTGACACACATTG TGCCCCTCTTCTTGGATGGCAACGTGTCCTTTCTGCCTGAAAACAGCTTCCCGAGCAGATTCCA GCCATTCCAGGATGGCTCCTCAGGGCAGAGGCGGCTGATTGCACTGCTTATGGCCTTTGTCTGC TCCCTGCCTCGAAATGGCAGCAGCTGGATGAATTCCTACAGCTAG CTGTGGACAAAGTGGAGGC TGGCCTGGACTCTGGGCCCTGTCGTAGTCAGGCCTTCACTCTTCTTCTCTGGGTAACAAAGGCC CTAGTGCTCAGATACCATCCTCTCAGCTCCTGCCTTACAGCCCGGCTCATGGGCCTCCTGAGTG ACCCAGAATTAGGTCCAGCAGCAGCTGATGGCTTCTCTCTGCTCATGTCTGACTGCACTGATGT GCTGACTCGTGCTGGCCATGCCGAAGTGCGGATCATGTTCCGCCAGCGGTTCTTCACAGATAAT GTGCCTGCTTTGGTCCAAGACTTCCATGCTGCTCCCCAAGATGTGAAGCCAAACTACTTGAAAG GTCTTTCTCATGTACTTAACAGGCTGCCCAAGCCTGTACTCTTGCCAGAGCTGCCCACGCTTCT TTCCTTGCTGCTGGAGGCCCTGTCCTGCCCTGACTGTGTGGTGCAGCTCTCCACCCTCAGCTGC CTTCAGCCTCTTCTACTGGAAGCACCCCAAGTCATGAGTCTTCACGTGGACACCCTCGTCACCA AGTTTCTGAACCTCAGCTCTAGCCCTTCCATGGCTGTCCGGATCGCCGCACTGCAGTGCATGCA TGCTCTCACTCGCCTGCCCACCCCTGTGCTGCTGCCGTACAAACCACAGGTGATTCGGGCCTTA GCCAAACCCCTGGATGACAAGAAGAGACTGGTGCGCAAGGAAGCAGTGTCAGCCAGAGGGGAGT GGTTTCTGTTGGGGAGCCCTGGCAGCTGAGCCCTCAGTCCTGGCCTAGACTGTTCTGACAATCT AACCTGGGATTACTAACTGTTGAGCCATCTTCCCCAAAGCAGGGAAACCACTGGTCTCTGACTG CCTTTCCCACAGACACAGCACAAATGCTAGGCCTCTGTTGCATGGCTGTACAAAGAACATAAGA GTCCATATTTCTAGTGGATTTGTAAAATAAGTGTGTGTGAGACACTTGCGTTTGAAGAAAGATC TAGGGTCCTGGGTCTCTTGCATTTATATGTCAGAAAAGGGGCGATATGCTGCTGAGGGGTGAGT GCATATGAGTGTGGCCCTGAGGACCAGGGCTGGCAGATGTTGTCTACCTGCTGAG ORF Start: ATG at 8                        ORF Stop: TAG at 2219 SEQ ID NO: 4                737 aa         MW at 813 17.6 kD NOV1b, MAAAAAVEAAAPMGALWGLVHDFVVGQQEGPADQVAADVKSGNYTVLQVVEALGSSLENPEPRT CG108030-02 Protein Sequence RARGIQLLSQVLLHCHTLLLEKEVVHLILFYENRLKDHHLVIPSVLQGLKALSLCVALPPGLAV SVLKAIFQEVHVQSLPQVDRHTVYNIITNFMRTREEELKSLGADFTFGFIQVMDGEKDPRNLLV AFRIVHDLISRDYSLGPFVEELFEVTSCYFPIDFTPPPNDPHGIQREDLILSLRAVLASTPRFA EFLLPLLIEKVDSEVLSAKLDSLQTLNACCAVYGQKELKDFLPSLWASIRREVFQTASERVEAE GLAALHSLTACLSRSVLRADAEDLLDSFLSNILQDCRHHLCEPDMKLVWPSASCCRQLQVHLPG PVTLSPAMYCLYCWNSSTSTVRAASGGTILEMLLGFLKLQQKWSYEDKDQRPLNGFKDQLCSLV FMALTDPSTQLQLVGIRTLTVLGAQPDLLSYEDLELAVGHLYRLSFLKEDSQSCRVAALEASGT LAALYPVAFSSHLVPKLAEELRVGESNLTNGDEPTQCSRHLCCLQALSAVSTHPSIVKETLPLL LQHLWQVNRGNMVAQSSDVIAVCQSLRQMAEKCQQDPESCWYFHQTAIPCLLALAVQASMPEKE PSVLRKVLLEDEVLAAMVSVIGTATTHLSPELAAQSVTHIVPLFLDGNVSFLPENSFPSRFQPF QDGSSGQRRLIALLMAFVCSLPRNGSSWMNSYS

[0351] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B. TABLE 1B Comparison of NOV1a against NOV1b. Identities/ NOV1a Residues/ Similarities for the Protein Sequence Match Residues Matched Region NOV1b 1 . . . 313 313/313 (100%) 416 . . . 728  313/313 (100%)

[0352] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C. TABLE 1C Protein Sequence Properties NOV1a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 11; pos. chg 2; neg. chg 0 H-region: length 3; peak value −19.72 PSG score: −24.12 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −3.97 possible cleavage site: between 40 and 41 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) . . . fixed PERIPHERAL Likelihood = 0.58 (at 232) ALOM score: 0.58 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 4.03 Hyd Moment(95): 7.41 G content: 1 D/E content: 2 S/T content: 1 Score: −7.36 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 7.2% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 76.7 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 47.8%: nuclear 26.1%: cytoplasmic 17.4%: mitochondrial  4.3%: vacuolar  4.3%: vesicles of secretory system >> indication for CG108030-01 is nuc (k = 23)

[0353] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1D. TABLE 1D Geneseq Results for NOV1a NOV1a Identities/ Geneseq Protein/Organism/Length [Patent #, Residues/ Similarities for Expect Identifier Date] Residues Region Value AAB61304 Human transcriptional regulator 1 . . . 378 376/378 (99%) 0.0 protein #4 - Homo sapiens, 615 aa. 1 . . . 378 376/378 (99%) [WO200078954-A2, 28 DEC. 2000] AAU28025 Novel human secretory protein, Seq 1 . . . 378 376/378 (99%) 0.0 ID No 194 - Homo sapiens, 666 aa. 52 . . . 429  376/378 (99%) [WO200166689-A2, 13 SEP. 2001] AAB93270 Human protein sequence SEQ ID 1 . . . 378 375/378 (99%) 0.0 NO: 12306 - Homo sapiens, 774 aa. 160 . . . 537  375/378 (99%) [EP1074617-A2, 07 FEB. 2001] AAM41729 Human polypeptide SEQ ID NO 6660 - 1 . . . 314  314/314 (100%) e−180 Homo sapiens, 398 aa. 67 . . . 380   314/314 (100%) [WO200153312-A1, 26 JUL. 2001] AAM39943 Human polypeptide SEQ ID NO 3088 - 1 . . . 314  314/314 (100%) e−180 Homo sapiens, 383 aa. 52 . . . 365   314/314 (100%) [WO200153312-A1, 26 JUL. 2001]

[0354] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E. TABLE 1E Public BLASTP Results for NOV1a NOV1a Identities/ Protein Residues/ Similarities Accession Match for the Expect Number Protein/Organism/Length Residues Matched Portion Value Q96T76 MMS19 - Homo sapiens (Human), 1 . . . 378 376/378 (99%) 0.0 1030 aa. 416 . . . 793  376/378 (99%) Q9BUE2 Hypothetical protein - Homo sapiens 1 . . . 378 376/378 (99%) 0.0 (Human), 692 aa (fragment). 78 . . . 455  376/378 (99%) Q9BYS9 MMS19 protein - Homo sapiens 1 . . . 378 376/378 (99%) 0.0 (Human), 1030 aa. 416 . . . 793  376/378 (99%) Q96DF1 MMS19 (MET18 S. cerevisiae)-like - 1 . . . 378 376/378 (99%) 0.0 Homo sapiens (Human), 666 aa. 52 . . . 429  376/378 (99%) Q96RK5 Transcriptional coactivator MMS19 - 1 . . . 378 375/378 (99%) 0.0 Homo sapiens (Human), 1030 aa. 416 . . . 793  375/378 (99%)

Example 2

[0355] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A. TABLE 2A NOV2 Sequence Analysis SEQ ID NO: 5               3058 bp NOV2a, GCCCCACAGTGAGACGAACGAAGGCAACAGTCGCCAGCAGCCGATGTGAAGACCGGACTCCGTG CG115907-01 DNA Sequence CGCCCCTCGCCGCCTCTGCCTGGCCACATCGATGTTGTGTCCGCCGCCTGCTCGCCCGGATCAC G ATGAAGCCCCCAAGGCCTGTCCGTACCTGCAGCAAAGTTCTCGTCCTGCTTTCACTGCTGGCC ATCCACCAGACTACTACTGCCGAAAAGAATGGCATCGACATCTACAGCCTCACCGTGGACTCCA GGGTCTCATCCCGATTTGCCCACACGGTCGTCACCAGCCGAGTGGTCAATAGGGCCAATACTGT GCAGGAGGCCACCTTCCAGATGGAGCTGCCCAAGAAAGCCTTCATCACCAACTTCTCCATGATC ATCGATGGCATGACCTACCCAGGGATCATCAAGGAGAAGGCTGAAGCCCAGGCACAGTACAGCG CAGCAGTGGCCAAGGGAAAGAGCGCTGGCCTCGTCAAGGCCACCGGGAGAAACATGGAGCAGTT CCAGGTGTCGGTCAGTGTGGCTCCCAATGCCAAGATCACCTTTGAGCTGGTCTATGAGGAGCTG CTCAAGCGGCGTTTGGGGGTGTACGAGCTGCTGCTGAAAGTGCGGCCCCAGCAGCTGGTCAAGC ACCTGCAGATGGACATTCACATCTTCGAGCCCCAGGGCATCAGCTTTCTGGAGACAGAGAGCAC CTTCATGACCAACCAGCTGGTAGACGCCCTCACCACCTGGCAGAATAAGACCAAGGCTCACATC CGGTTCAAGCCAACACTTTCCCAGCAGCAAAAGTCCCCAGAGCAGCAAGAAACAGTCCTGGACG GCAACCTCATTATCCGCTATGATGTGGACCGGGCCATCTCCCCGGGCTCCATTCAGATCGAGAA CGGCTACTTTGTACACTACTTTGCCCCCCAGGGCCTAACCACAATGCCCAAGAATGTGGTCTTT GTCATTGACAAGAGCGGCTCCATGAGTGGCAGGAAAATCCAGCAGACCCGGGAAGCCCTAATCA AGATCCTGGATGACCTCAGCCCCAGAGACCAGTTCAACCTCATCGTCTTCAGTACAGAAGCAAC TCAGTGGAGGCCATCACTGGTGCCAGCCTCAGCCGAGAACGTGAACAAGGCCAGGAGCTTTGCT GCGGGCATCCAGGCCCTGGGAGGGACCAACATCAATGATGCAATGCTGATGGCTGTGCAGTTGC TGGACAGCAGCAACCAGGAGGAGCGGCTGCCCGAAGGGAGTGTCTCACTCATCATCCTGCTCAC CGATGGCGACCCCACTGTGGGGGAGACTAACCCCAGGAGCATCCAGAATAACGTGCGGGAAGCT GTAAGTGGCCGGTACAGCCTCTTCTCCCTGCGCTTCGGTTTCGACGTCAGCTATGCCTTCCTGG AGAAGCTGGCACTGGACAATGGCGGCCTGGCCCGGCGCATCCATGAGGACTCAGACTCTGCCCT GCAGCTCCAGGACTTCTACCAGGAAGTGAGCGACCCACTGCTGACAGCAGTGACCTTCGAGTAC CCAAGCAATGCCGTGGAGGAGGTCACTCAGAACAACTTCCGGCTCCTCTTCAAGGGCTCAGAGA TGGTGGTGGCTGGGAAGCTCCAGGACCGGGGGCCTGATGTGCTCACAGCCACAGTCAGTGGGAA GCTGCCTACACAGAACATCACTTTCCAAACGGAGTCCAGTGTGGCAGAGCAGGAGGCGGAGTTC CAGAGCCCCCAAGTATATCTTCCACAACTTCATGGAGAGGCTCTGGGATACCTGACTATCCAGC AGCTGCTGGAGCAAACTGTCTCCGCATCCGATGCTGATCAGGCAGGCCCTCCGAACCAAGCGCT GAATTTATCACTTGCCTACAGCTTTGTCACGCCTCTCACATCTATGGTAGTCACCAAACCCGAT GACCAAGAGCAGTCTCAAGTTGCTGAGAAGCCCATGGAAGGCGAAAGTAGAAACAGGAATGTCC ACTCAGGTTCCACTTTCTTCAAATATTATCTCCAGGGAGCAAAAATACCAAAACCAGAGGCTTC CTTTTCTCCAAGAAGAGGATGGAATAGACAAGCTGGAGCTGCTGGCTCCCGGATGAATTTCAGA CCTGGGGTTCTCAGCTCCAGGCAACTTGGACTCCCAGGACCTCCTGATGTTCCTGACCATGCTG CTTACCACCCCTTCCGCCGTCTGGCATCCTTGCCTGCTTCAGCACCACCAGCCACCTCAAATCC TGATCCAGCTGTGTCTCGTGTCATGAATATGAAAATCGAAGAAACAACCATGACAACCCAAACC CCAGCCCCCATACAGGCTCCCTCTGCCATCCTGCCACTGCCTGGGCAGAGTGTGGAGCGGCTCT GTGTGGACCCCAGACACCGCCAGGGGCCAGTGAACCTGCTCTCAGACCCTGAGCAAGGGGTTGA GGTGACTGGCCAGTATGAGAGGGAGAAGGCTGGGTTCTCATGGATCGAAGTGACCTTCAAGAAC CCCCTGGTATGGGTTCACGCATCCCCTGAACACGTGGTGGTGACTCGGAACCGAAGAAGCTCTG CGTACAAGTGGAAGGAGACGCTATTCTCAGTGATGCCCGGCCTGAAGATGACCATGGACAAGAC GGGTCTCCTGCTGCTCAGTGACCCAGACAAGTCACCATCGGCCCTGTTGTTCTGGGATGGCCGT GGGGAGGGGCTCCGGCTCCTTCTGCGTGACACTGACCGCTTCTCCAGCCACGTTGGAGGGACCC TTGGCCAGTTTTACCAGGAGGTGCTCTGGGGATCTCCAGCAGCATCAGATGACGGCAGACGCAC GCTGAGGGTTCAGGGCAATGACCACTCTGCCACCAGAGAGCGCAGGCTGGATTACCAGGAGGGG CCCCCGGGAGTGGAGATTTCCTGCTGGTCTGTGGAGCTGTAG TTCTGATGGAAGGAGCTGTGCC CACCCTGTACACTTGGCTTCCCCCTGCAACTGCAGGGCCGCTTCTGGGGCCTGGACCACCATGG GGAGGAAGAGTCCCACTCATTACAAATAAAGAAAGGTGGTGTGAGCCTGA ORF Start: ATG at 130                      ORF Stop: TAG at 2920 SEQ ID NO: 6                930 aa         MW at 103356.4 kD NOV2a, MKPPRPVRTCSKVLVLLSLLAIHQTTTAEKNGIDIYSLTVDSRVSSRFAHTVVTSRVVNRANTV CG115907-01 Protein Sequence QEATFQMELPKKAFITNFSMIIDGMTYPGIIKEKAEAQAQYSAAVAKGKSAGLYKATGRNMEQF QVSVSVAPNAKITFELVYEELLKRRLGVYELLLKVRPQQLVKHLQMDIHIFEPQGISFLETEST FMTNQLVDALTTWQNKTKAHIRFKPTLSQQQKSPEQQETVLDGNLIIRYDVDRAISGGSIQIEN GYFVHYFAPEGLTTMPKNVVFVIDKSGSMSGRKIQQTREALIKILDDLSPRDQFNLIVFSTEAT QWRPSLVPASAENVNKARSFAAGIQALGGTNINDANLMAVQLLDSSNQEERLPEGSVSLIILLT DGDPTVGETNPRSIQNNVREAVSGRYSLFCLGFGFDVSYAFLEKLALDNGGLARRIHEDSDSAL QLQDFYQEVANPLLTAVTFEYPSNAVEEVTQNNFRLLFKGSEMVVAGKLQDRGPDVLTATVSGK LPTQNITFQTESSVAEQEAEFQSPKYIFHNFMERLWAYLTIQQLLEQTVSASDADQQALRNQAL NLSLAYSFVTPLTSMVVTKPDDQEQSQVAEKPMEGESRNRNVHSGSTFFKYYLQGAKIPKPEAS FSPRRGWNRQAGAAGSRMNFRPGVLSSRQLGLPGPPDVPDHAAYHPFRRLAILPASAPPATSNP DPAVSRVMNMKIEETTMTTQTPAPIQAPSAILPLPGQSVERLCVDPRHRQGPVNLLSDPEQGVE VTGQYEREKAGFSWIEVTFKNPLVWVHASPEHVVVTRNRRSSAYKWKETLFSVMPGLKMTMDKT GLLLLSDPDKVTIGLLFWDGRGEGLRLLLRDTDRFSSHVGGTLGQFYQEVLWGSPAASDDGRRT LRVQGNDHSATRERRLDYQEGPPGVEISCWSVEL SEQ ID NO: 7               2797 bp NOV2b, GCCCCACAGTGAGAGGAAGGAAGGCAACAGTCGCCAGCAGCCGATGTGAAGACCGGACTCCGTG CG115907-04 DNA Sequence CGCCCCTCGCCGCCTCTGCCTGGCCACATCGATGTTGTGTCCGCCGCCTGCTCGCCCGGATCAC G ATGAAGCCCCCAAGGCCTGTCCGTACCTGCAGCAAAGTTCTCGTCCTGCTTTCACTGCTGGCC ATCCACCAGACTACTACTGCCGAAAAGAATGGCATCGACATCTACAGCCTCACCGTGGACTCCA GGGTCTCATCCCGATTTGCCCACACGGTCGTCACCAGCCGAGTGGTCAATAGGGCCAATACTGT GCAGGAGGCCACCTTCCAGATGGAGCTGCCCAAGAAAGCCTTCATCACCAACTTCTCCATGATC ATCGATGGCATGACCTACCCAGGGATCATCAAGGAGAAGGCTGAAGCCCAGGCACAGTACAGCG GAGCAGTGGCCAAGGGAAAGAGCGCTGGCCTCGTCAAGGCCACCGGGAGAAACATGGAGCAGTT CCAGGTGTCGGTCAGTGTGGCTCCCAATGCCAAGATCACCTTTGAGCTGGTCTATGAGGAGCTG CTCAAGCGGCGTTTGGGGGTGTACGAGCTGCTGCTGAAAGTGCGGCCCCAGCAGCTGGTCAAGC ACCTGCAGATGGACATTCACATCCTCGAGCCCCAGGGCATCAGCTTTCTGGAGACAGAGAGCAC CTTCATGACCAACCAGCTGGTAGACGCCCTCACCACCTGGCAGAATAAGACCAAGGCTCACATC CGGTTCAAGCCAACACTTTCCCAGCAGCAAAAGTCCCCAGAGCAGCAAGAAACAGTCCTGGACG GCAACCTCATTATCCGCTATGATGTGGACCGGGCCATCTCCGGGGGCTCCATTCAGATCGAGAA CGGCTACTTTGTACACTACTTTGCCCCCGAGGGCCTAACCACAATGCCCAAGAATGTGGTCTTT GTCATTGACAAGAGCGGCTCCATGAGTGGCAGGAAAATCCAGCAGACCCGGGAAGCCCTAATCA AGATCCTGGATGACCTCAGCCCCAGAGACCAGTTCAACCTCATCGTCTTCAGTACAGAAGCAAC TCAGTGGAGGCCATCACTGGTGCCAGCCTCAGCCGAGAACGTGAACAAGGCCAGGAGCTTTGCT GCGGGCATCCAGGCCCTGCGAGGGACCAACATCAATGATGCAATGCTGATGGCTGTGCAGTTGC TGGACAGCAGCAACCAGGAGGAGCGGCTGCCCGAAGGGAGTGTCTCACTCATCATCCTGCTCAC CGATGGCGACCCCACTGTGGGGGAGACTAACCCCAGGAGCATCCAGAATAACGTGCGGGAAGCT GTAAGTGGCCGTACAGCCTCTTCTGCCTGGGCTTCGGTTTCGAACGTCAGCTATGCCTTCCTGG AGAAGCTGGCACTGGACAATGGCGGCCTGGCCCGGCGCATCCATGAGGACTCAGACTCTGCCCT GCAGCTCCAGGACTTCTACCAGGAAGTGGCCAACCCACTGCTGACAGCAGTGACCTTCGAGTAC CCAAGCAATGCCGTGGAGGAGGTCACTCAGAACAACTTCCGGCTCCTCTTCAAGGGCTCAGAGA TGGTGGTGGCTGGGAAGCTCCAGGACCGGGGGCCTGATGTGCTCACAGCCACAGTCAGTGGGAA GCTGCCTACACAGAACATCACTTTCCAAACGGAGTCCAGTGTGGCAGAGCAGGAGGCGGAGTCC CAGAGCCCCAAGTATATCTTCCACAACTTCATGGAGAGGCTCTGGGCATACCTGACTATCCAGC AGCTGCTGGAGCAAACTGTCTCCGCATCCGATGCTGATCAGCAGGCCCTCCGGAACCAAGCGCT GAATTTATCACTTGCCTACAGCTTTGTCACGCCTCTCACATCTATGGTAGTCACCAAACCCGAT GACCAAGAGCAGTCTCAAGTTGCTGAGAAGCCCATGGAAGGCGAAAGTAGAAACAGGAATGTCC ACTCAGCTGGAGCTGCTGGCTCCCGGATGAATTTCAGACCTGGGGTTCTCAGCTCCAGGCAACT TGGACTCCCAGGACCTCCTGATGTTCCTGACCATGCTGCTTACCACCCCTTCCGCCGTCTGGCC ATCTTGCCTGCTTCAGCACCACCAGCCACCTCAAATCCTGATCCAGCTGTGTCTCGTGTCATGA ATATGCAGTATGAGAGGGAGAAGGCTCGGTTCTCATGCATCGAAGTGACCTTCAAGAACCCCCT GGTATGGGTTCACGCATCCCCTGAACACGTGGTGGTGACTCGGAACCGAAGAAGCTCTGCGTAC AAGTGGAAGGAGACGCTATTCTCAGTGATGCCCGGCCTGAAGATGACCATGGACAAGACGGGTC TCCTGCTGCTCAGTGACCCAGACAAAGTGACCATCGGCCTGTTGTTCTGGGATGGCCGTGGGGA GGGGCTCCGGCTCCTTCTGCGTGACACTGACCGCTTCTCCAGCCACGTTGGAGGGACCCTTGGC CAGTTTTACCAGGAGGTGCTCTGGGGATCTCCAGCAGCATCAGATGACGGCAGACGCACGCTGA GGGTTCAGGGCAATGACCACTCTGCCACCAGAGAGCGCAGGCTGGATTACCAGGAGGGGCCCCC GGGAGTGGAGATTTCCTGCTCGTCTGTGGAGCTGTAG TTCTGATGGAAGGAGCTGTGCCCACCC TGTACACTTGGCTTCCCCCTGCAACTGCAGGGCCGCTTCTGGGGCCTGGACCACCATGGGGAGG AAGAGTCCCACTCATTACAAATAAAGAAAGGTGGTGTGAGCCTGA ORF Start: ATG at 130                      ORF Stop: TAG at 2659 SEQ ID NO: 8                843 aa         MW at 93770.6 kD NOV2b, MKPPRPVRTCSKVLVLLSLLAIHQTTTAEKNGIDIYSLTVDSRVSSRFAHTVVTSRVVNRANTV CG115907-04 Protein Sequence QEATFQMELPKKAFITNFSMIIDGMTYPGIIKEKAEAQAQYSAAVAKGKSAGLVKATGRNMEQF QVSVSVAPNAKITFELVYEELLKRRLGVYELLLKVRPQQLVKHLQMDIHIFEPQGISFLETEST FMTNQLVDALTTWQNICTKAHIRFKPTLSQQQKSPEQQELLDGNLIIRYDVDRATSGGSIQIEN GYFVHYFAPEGLTTMPKNVVFVIDKSGSMSGRKIQQTREALIKILDDLSPRDQFNLIVFSTEAT QWRPSLVPASAENVNKARSFAAGIQALGGTNINDAMLMAVQLLDSSNQEERLPEGSVSLIILLT DGDPTVGETNPRSIQNNVREAVSGRYSLFCLGFGFDVSYAFLEKLALDNGGLARRIHEDSDSAL QLQDFYQEVANPLLTAVTFEYPSNAVEEVTQNNFRLLFKGSEMVVAGKLQDRGPDVLTATVSGK LPTQNITFQTESSVAEQEAEFQPKYIFHNFMERLWAYLTIQQLLEQTVSAASDADQQALRNQAL NLSLAYSFVTPLTSMVVTKPDDQEQSQVAEKPMEGESRNRNVHSAGAAGSRMNFRPGVLSSRQL GLPGPPDVPDHAAYHPFRRLAILPASAPPATSNPDPAVSRVMNMQYEREKAGFSWIEVTFKNPL VWVHASPEHVVVTRNRRSSAYKWKETLFSVMPGLRDTMDKTGLLLLSDPDKVTIGLLFWDGRGE GLRLLLRDTDRFSSHVGGTLGQFYQEVLWGSPAASDDGRRTLRVQGNDHSATRERRLDYQSGPP GVEISCWSVEL SEQ ID NO: 9               2914 bp NOV2c, GCCCCACAGTGAGAGGAAGGAAGGCAACAGTCGCCAGCAGCCGATGTGAAGACCGGACTCCGTG CG115907-03 DNA Sequence CGCCCCTCGCCGCCTCTGCCTGGCCACATCGATGTTGTGTCCGCCGCCTGCTCGCCCGGATCAC G ATGAAGCCCCCAACGCCTGTCCGTACCTGCAGCAAAGTTCTCGTCCTGCTTTCACTGCTGGCC ATCCACCAGACTACTACTGCCGAAAAGAATGGCATCGACATCTACAGCCTCACCGTGGACTCCA GGGTCTCATCCCGATTTGCCCACACGGTCGTCACCAGCCGAGTGGTCAATAGGGCCAATACTGT GCAGGAGGCCACCTTCCAGATGGAGCTGCCCAAGAAAGCCTTCATCACCAACTTCTCCATGATC ATCGATGGCATGACCTACCCAGGGATCATCAAGGAGAAGGCTGAAGCCCAGGCACAGTACAGCG CAGCAGTCGCCAAGGGAAAGAGCGCTGGCCTCGTCAAGGCCACCGGGACAAACATCGAGCAGTT CCAGGTGTCGGTCAGTGTGGCTCCCAATGCCAAGATCACCTTTGAGCTGGTCTATGAGGAGCTG CTCAAGCGGCGTTTGGGGGTGTACGAGCTGCTGCTGAAAGTGCGGCCCCAGCAGCTGGTCAAGC ACCTGCAGATGGACATTCACATCTTCGAGCCCCAGGGCATCAGCTTTCTGGAGACAGAGAGCAC CTTCATGACCAACCAGCTGGTAGACGCCCTCACCACCTCGCAGAATAAGACCAAGGCTCACATC CGGTTCAAGCCAACACTTTCCCAGCAGCAAAAGTCCCCAGAGCAGCAAGAAACAGTCCTGGACG GCAACCTCATTATCCGCTATGATGTGGACCGGGCCATCTCCGGGGGCTCCATTCAGATCGAGAA CGGCTACTTTGTACACTACTTTGCCCCCGACGGCCTAACCACAATGCCCAAGAATGTCGTCTTT GTCATTGACAAGAGCGGCTCCATGAGTGGCAGGAAAATCCAGCAGACCCGGGAAGCCCTAATCA AGATCCTGGATGACCTCAGCCCCAGAGACCAGTTCAACCTCATCGTCTTCAGTACAGAAGCAAC TCAGTGGAGGCCATCACTGGTGCCAGCCTCAGCCGAGAACGTGAACAAGGCCAGGAGCTTTGCT GCGGGCATCCAGCCCCTGGGAGGGACCAACATCAATGATGCAATGCTGATGGCTGTGCAGTTGC TGGACAGCAGCAACCAGGAGGAGCGGCTGCCCGAAGGGAGTGTCTCACTCATCATCCTGCTCAC CGATGGCGACCCCACTGTGGGGGAGACTAACCCCAGGAGCATCCAGAATAACGTGCGGGAAGCT GTAAGTGGCCGGTACAGCCTCTTCTGCCTGGGCTTCGGTTTCGACGTCAGCTATGCCTTCCTGG AGAAGCTGGCACTGGACAATCGCCGCCTGGCCCGGCGCATCCATGACGACTCAGACTCTGCCCT GCAGCTCCACGACTTCTACCAGGAAGTGGCCAACCCACTGCTGACAGCAGTGACCTTCGAGTAC CCAAGCAATGCCGTGGACGAGGTCACTCAGAACAACTTCCGGCTCCTCTTCAAGGGCTCAGAGA TGGTCGTGGCTGGGAAGCTCCAGACCGGGGCGCCTGATGTGCTCACAGCCACAGTCAGTGGGAA GCTGCCTACACAGAACATCACTTTCCAAACGGAGTCCAGTGTGGCAGAGCAGGAGGCGGAGTTC CAGAGCCCCAAGTATATCTTCCACAACTTCATGGAGAGGCTCTGGGCATACCTGACTATCCAGC AGCTGCTCGAGCAAACTGTCTCCGCATCCGATGCTGATCAGCAGGCCCTCCGGAACCAAGCGCT GAATTTATCACTTGCCTACAGCTTTGTCACGCCTCTCACATCTATGGTAGTCACCAAACCCGAT GACCAAGAGCAGTCTCAGTTGCTGAGAAGCCCATGGAAGGCGAAAGTACAAACAGGGAATGTCC ACTCAGCTCGAGCTGCTGGCTCCCGGATGAATTTCAGACCTGGGGTTCTCAGCTCCAGGCAACT TGGACTCCCAGGACCTCCTGATGTTCCTGACCATGCTGCTTACCACCCCTTCCGCCGTCTGGCC ATCTTGCCTGCTTCAGCAACACCAGCCACCTCAAATCCTGATCCAGCTGTGTCTCGTGTCATGA ATATGTCTGCCATCCTGCCACTGCCTGGGCAGGTGTGGAGCGGCTCTGTGTGGACCCCCAGACA CCGCCAGGGGCCAGTGAACCTGCTCTCAGACCCTGAGCAAGGGGTTGAGGTGACTGGCCAGTAT GAGAGGGAGAAGGCTCGGTTCTCATGGATCGAAGTGACCTTCAAGAACCCCCTGGTATGGGTTC ACGCATCCCCTGAACACGTGGTGGTGACTCGGAACCGAAGAAGCTCTGCGTACAAGTGGAAGGA GACGCTATTCTCAGTGATGCCCCGCCTGAAGATGACCATGGACAAGACGGGTCTCCTGCTGCTC AGTGACCCAGACAAAGTGACCATCGGCCTGTTGTTCTGCGATGGCCGTGGGGAGGGGCTCCGGC TCCTTCTGCGTGACACTCACCGCTTCTCCAGCCACGTTGGACGGACCCTTGGCCAGTTTTACCA GGAGGTGCTCTGGGGATCTCCAGCAGCATCAGATGACGGCAGACGCACGCTGAGGGTTCAGGGC AATGACCACTCTGCCACCAGAGAGCGCAGGCTGGATTACCACGACGGGCCCCCGGGAGTGGAGA TTTCCTGCTCGTCTGTGGAGCTCTAG TTCTGATGGAAGGAGCTGTGCCCACCCTGTACACTTGG CTTCCCCCTGCAACTGCAGGGCCGCTTCTGGGGCCTGGACCACCATGGGGAGGAAGAGTCCCAC TCATTACAAATAAAGAAAGGTGGTGTGAGCCTGA ORF Start: ATG at 130                      ORF Stop: TAG at 2776 SEQ ID NO: 10               882 aa         MW at 97921.2 kD NOV2c, MKPPRPVRTCSKVLVLLSLLAIHQTTTAEKNGIDIYSLTVDSRVSSRFAHTVVTSRVVNRANTV CG115907-03 Protein Sequence QEATFQMELPKKAFITNFSMIIDGMTYPGIIKEKAEAQAQYSAAVAKGKSAGLVKATGRNMEQF QVSVSVAPNAKITEELVYEELLKRRLGVYELLLKVRPQQLVKHLQMDIHIFEPQGISFLETEST FMTNQLVDALTTWQNKTKAHIRFKPTLSQQQKSFEQQETVLDGNLIIRYDVDRAISGGSIQIEN GYFVHYFAKPEGLTTMPKNVVFVIDKSGSMSGRKIQQTREALIKILDDLSPRDFNLIVFSTEAT QWRPSLVPASAENVNCARSFAAGIQALGGTNINDAMLMAVQLLDSSNQEERLPEGSVSLIILLT DGDPTVGETNPRSIQNNVREAVSGRYSLFCLGFGFDVSYAFLEKLALDNGGLARRIHEDSDSAL QLQDFYQEVANPLLTAVTFEYPSNAVEEVTGNNFRLLFKGSEMVVAGKLQDRGPDVLTATVSGK LPTQNITFQTESSVAEQEAEFQSPKYIFHNFMERLWAYLTIQQLLEQTVSASDADQQALRNQAL NLSLAYSFVTPLTSMVVTKPDDQEQSQVAEKPMEGESRNRNVHSAGAAGSRMNFRPGVLSSRQL GLPGPPDVPDHAAYHPFRRLATLPASATPATSNPDPAVSRVMNMSAILPLPGQSVERLCVDPRH RQGPVNLLSDPEQGVEVTCGYEREKAGFSWIEVTFKNPLVWVHASPEHVVVTRNRRSSAYKWKE TLFSVMPGLKMTMDKTGLLLLSDPDKVTIGLLFWDGRGEGLRLLLRDTDRFSSHVGGTLGQFYQ EVLWGSPAASDDGRRTLRVQGNDHSATRERRLDYQEGPPGVEISCWSVEL SEQ ID NO: 11               968 bp NOV2d, CGCCCCTCGCCGCCTCTGCCTGGCCACATCGATGTTGTGTCCCCCGCCTGCTCGCCCCGATCAC CG115907-02 DNA Sequence CGCCCCTCGCCGCCTCTGCCTGGCCACATCGATGTTGTGTCCGCCGCCTGCTCGCCCGGATCAC G ATGAAGCCCCCAAGGCCTGTCCGTACCTGCAGCAAAGTTCTCGTCCTGCTTTCACTGCTGGCC ATCCACCAGACTACTACTGCCGAAAAGAATGGCATCGACATCTACAGCCTCACCGTGGACTCCA GGGTCTCATCCCGATTTGCCCACACGGTCGTCACGAGCCGAGTGGTCAATAGGGCCAATACTGT GCAGGAGGCCACCTTCCAGATGGAGCTGCCCAAGAAAGCCTTCATCACCAACTTCTCCATGATC ATCGATGGCATGACCTACCCAGGGATCATCAAGGAGAAGGCTGAAGCCCAGGCACAGTACAGCG CAGCAGTCGCCAAGGGAAAGAGCGCTGGCCTCGTCAAGGCCACCGGGAGAAACATGGAGCAGTT CCAGGTGTCCGTCAGTGTGGCTCCCAATGCCAAGATCACCTTTGAGCTGGTCTATGAGGAGCTG CTCAAGCGGCGTTTGGGGGTGTACGAGCTGCTGCTGAAAGTGCGGCCCCAGCAGCTGGTCAAGC ACCTGCAGATGGACATTCACATCTTCGAGCCCCAGGGCATCAGCTTTCTGGAGACAGAGAGCAC CTTCATGACCAACCAGCTGGTAGACGCCCTCACCACCTGGCAGAATAAGACCAAGGCTCACATC CGGTTCAAGCCAACACTTTCCCAGCAGCAAAAGTCCCCAGAGCAGCAAGAAACAGTCCTGGACG GCAACCTCATTATCCGCTATGATGTGGACCGGGCCATCTCCGGGGGCTCCATTCAGATCGAGAA CGGCTACTTTGTACACTACTTTGCCCCCGAGGGCCTAACCACAATGCCCAAGAATGTGGTCTTT GTCATTGACAAGAGCGGCTCCATGAGTGGCAGGAAAATCCAGCAGACCCGGGAAGCCCTAATCA AGATCCTGGATGACCTCAGCCCCAGAGACCACTTCAACCTCATCGTCTTCAGTACAGAAGCAAC TCAGTGGAGGCCATCACTGGTGCCAGCCTCAGCCGAGAACGTGAACAAGGCCAGGAGCTTTGCT GCGGGCATCCAGCCCCTCGGAGGGACCAACATCAATGATGCAATGCTGATGGCTGTGCAGTTGC TGGACAGCAGCAACCAGGAGGAGCGGCTGCCCGAAGGGAGTGTCTCACTCATCATCCTGCTCAC CGATGGCGACCCCACTGTGGGGGAGACTAACCCCAGGAGCATCCAGAATAACGTGCGGGAAGCT GTAAGTGGCCGGTACAGCCTCTTCTGCCTGGGCTTCGGTTTCGACGTCAGCTATGCCTTCCTGG AGAAGCTGGCACTGGACAATGGCCGCCTGGCCCGGCGCATCCATGAGGACTCAGACTCTGCCCT GCAGCTCCAGGACTTCTACCAGGAAGTGGCCAACCCACTGCTGACAGCAGTGACCTTCGAGTAC CCAAGCAATGCCGTGGAGGAGGTCACTCAGAACAACTTCCGGCTCCTCTTCAAGGGCTCAGAGA TGGTGGTGGCTGGGAAGCTCCAGGACCGGGCGCCTGATGTGCTCACAGCCACAGTCAGTGGGAA GCTGCCTACACAGAACATCACTTTCCAAACGGAGTCCAGTGTGGCAGAGCAGGAGGCGGAGTTC CAGAGCCCCAAGTATATCTTCCACAACTTCATGGAGAGGCTCTGGGCATACCTGACTATCCAGC AGCTGCTGGAGCAAACTGTCTCCGCATCCGATGCTGATCAGCAGGCCCTCCGGAACCAAGCGCT GAATTTATCACTTGCCTACAGCTTTGTCACGCCTCTCACATCTATGGTAGTCACCAAACCCGAT GACCAAGACCAGTCTCAAGTTGCTGAGAAGCCCATGGAAGGCGAAAGTAGAAACAGGAATGTCC ACTCAGCTGGAGCTGCTCGCTCCCGGATGAATTTCAGACCTGGGGTTCTCAGCTCCAGGCAACT TGGACTCCCAGGACCTCCTGATGTTCCTGACCATGCTGCTTACCACCCCTTCCGCCGTCTGGCC ATCTTGCCTGCTTCAGCACCACCAGCCACCTCAAATCCTGATCCAGCTGTGTCTCGTGTCATGA ATATGAAAATCGAAGAAACAACCATGACAACCCAAACCCCAGCCCCCATACAGGCTCCCTCTGC CATCCTGCCACTGCCTGGGCAGAGTGTGGAGCGGCTCTGTGTGGACCCCAGACACCGCCAGGGG CCAGTGAACCTGCTCTCAGACCCTGAGCAAGGGGTTGAGGTGACTCGCCAGTATGACAGGGAGA AGGCTGCGTTCTCATGGATCGAAGTGACCTTCAAGAACCCCCTGGTATGGGTTCACGCATCCCC TGAACACGTGGTGGTGACTCGGAACCGAAGAAGCTCTGCGTACAAGTGGAAGGAGACGCTATTC TCAGTGATGCCCGGCCTGAAGATGACCATGGACAAGACGGGTCTCCTGCTGCTCAGTGACCCAG ACAAAGTGACCATCGGCCTGTTGTTCTGGGATGGCCGTGGGGAGGGGCTCCGGCTCCTTCTGCG TGACACTGACCGCTTCTCCAGCCACGTTGGAGGGACCCTTGGCCAGTTTTACCAGGAGGTGCTC TCGGGATCTCCAGCAGCATCAGATGACGGCAGACGCACGCTGACGGTTCAGGGCAATGACCACT CTGCCACCAGAGAGCGCAGGCTCGATTACCAGGAGGCGCCCCCGGGAGTGGAGATTTCCTGCTG GTCTGTGGAGCTGTAG TTCTGATGGAGGAGCTGTGCCCACCCTGTACACTTGGCTTCCCCCCTG CAACTGCAGGGCCGCTTCTGGGGCCTGGACCACCATGGGGAGGAAGAGTCCCACTCATTACAAA TAAAGAAAGGTGGTGTGAGCCTCA ORF Start: ATG at 130                      ORF Stop: TAG at 2830 SEQ ID NO: 12               900 aa         MW at 99856.4kD NOV2d, MKPPRPVRTCSKVLVLLSLLAIHQTTTAEKNGIDIYSLTVDSRVSSRFAHTVVTSRVVNRANTV CG115907-02 Protein Sequence QEATFQMELPKKAFITNFSMIIDGMTYPGIIKEKAEAGAQYSAAVAKGKSAGLVKATGRNMEQF QVSVSVAPNAKITFELVYEELLKRRLGVYELLLKVRPQQLVKHLQMDIHIFEPQGISFLETEST FMTNQLVDALTTWQNKTKAHIRFKPTLSQQQKSPEQQETVLDGNLITRYDVDRAISGGSIQIEN GYFVHYFAPEGLTTMPKNVVFVIDKSGSMSGRKIQQTREALIKILDDLSPRDQFNLIVFSTEAT QWRPSLVPASAENVNKARSFAAGIQALGGTNINDAMLMAVQLLDSSNQEERLPEGSVSLIILLT DGDPTVGETNPRSIQNNVREAVSGRYSLFCLGFGFDVSYAFLEKLALDNGGLARRIHEDSDSAL QLQDFYQEVANPLLTAVTFEYPSNAVEEVTQNNFRLLFKGSEMVVAGKLQDRGPDVLTATVSGK LPTQNITFQTESSVAEQEAEFQSPKYIFHNFMERLWAYLTIQQLLEQTVSASDADQQALRNQAL NLSLAYSFVTPLTSMVVTKPDDQEQSQVAEKPMEGESRNRNVHSAGAAGSRMNFRPGVLSSRQL GLPGPPDVPDHAAYHPFRRLAILPASAPPATSNPDPAVSRVMNMKIEETTMTTQTPAPIQAPSA ILPLPGQSVERLCVDPRHRQGPVNLLSDPEQGVEVTGQYEREKAGFSWIEVTFKNPLVWVHASP EHVVVTRNRRSSAYKWKETLFSVMPGLKMTMDKTGLLLLSDPDKVTIGLLFWDGRGEGLRLLLR DTDRFSSHVGGTLGQFYQEVLWGSPAASDDGRRTLRVQGNDHSATRERRLDYQEGPPGVEISCW SVEL

[0356] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B. TABLE 2B Comparison of NOV2a against NOV2b through NOV2d. Identities/ NOV2a Residues/ Similarities for the Protein Sequence Match Residues Matched Region NOV2b 1 . . . 930 804/930 (86%) 1 . . . 843 813/930 (86%) NOV2c 1 . . . 930 881/930 (94%) 1 . . . 882 881/930 (94%) NOV2d 1 . . . 930 900/930 (96%) 1 . . . 900 900/930 (96%)

[0357] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C. TABLE 2C Protein Sequence Properties NOV2a SignalP Cleavage site between residues 29 and 30 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 8; pos. chg 3; neg. chg 0 H-region: length 3; peak value 3.04 PSG score: −1.36 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 0.51 possible cleavage site: between 27 and 28 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 2.01 (at 578) ALOM score: −0.64 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 3.74 Hyd Moment(95): 8.90 G content: 0 D/E content: 1 S/T content: 6 Score: −1.36 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 18 VRT|CS NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.4% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: KPPR none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 70.6 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 60.9%: mitochondrial  8.7%: cytoplasmic  8.7%: extracellular, including cell wall  8.7%: peroxisomal  4.3%: vacuolar  4.3%: Golgi  4.3%: nuclear >> indication for CG115907-01 is mit (k = 23)

[0358] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D. TABLE 2D Geneseq Results for NOV2a NOV2a Identities/ Residues/ Similarities for Geneseq Protein/Organism/Length [Patent #, Match the Matched Expect Identifier Date] Residues Region Value ABB09709 Amino acid sequence of a human 1 . . . 930  930/930 (100%) 0.0 PK-120 polypeptide - Homo sapiens, 1 . . . 930  930/930 (100%) 930 aa. [WO200212495-A1, 14 FEB. 2002] ABB09708 Sequence of H4P heavy chain of inter 1 . . . 930 928/930 (99%) 0.0 alpha trypsin inhibitor - Homo sapiens, 1 . . . 930 929/930 (99%) 930 aa. [WO200212495-A1, 14 FEB. 2002] ABB09711 Sequence of H4P heavy chain of 13 . . . 930  663/924 (71%) 0.0 inter-alpha-inhibitor protein - Sos sp, 12 . . . 921  758/924 (81%) 921 aa. [WO200212495-A1, 14 FEB. 2002] ABB09707 Sequence of H4P heavy chain of 1 . . . 930 615/941 (65%) 0.0 inter-alpha-inhibitor protein - Rattus 1 . . . 933 728/941 (77%) sp, 933 aa. [WO200212495-A1, 14 FEB. 2002] ABB09706 Sequence of H4P heavy chain of 1 . . . 930 600/941 (63%) 0.0 inter-alpha-inhibitor protein - Rattus 1 . . . 932 715/941 (75%) sp, 932 aa. [WO200212495-A1, 14 FEB. 2002]

[0359] In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E. TABLE 2E Public BLASTP Results for NOV2a NOV2a Identities/ Protein Residues/ Similarities for Accession Match the Matched Expect Number Protein/Organism/Length Residues Portion Value Q14624 Inter-alpha-trypsin inhibitor heavy chain 1 . . . 930 929/930 (99%) 0.0 H4 precursor (ITI heavy chain H4) 1 . . . 930 929/930 (99%) (Inter-alpha-inhibitor heavy chain 4) (Inter-alpha-trypsin inhibitor family heavy chain-related protein) (IHRP) (Plasma kallikrein sensitive glycoprotein 120) (PK-120) (GP120) (PRO1851) [Contains: GP57] - Homo sapiens (Human), 930 aa. JX0368 inter-alpha-trypsin inhibitor heavy 1 . . . 930 928/930 (99%) 0.0 chain-related protein precursor - human, 1 . . . 930 929/930 (99%) 930 aa. P79263 Inter-alpha-trypsin inhibitor heavy chain 13 . . . 930  663/924 (71%) 0.0 H4 precursor (ITI heavy chain H4) 12 . . . 921  758/924 (81%) (Inter-alpha-inhibitor heavy chain 4) (Inter-alpha-trypsin inhibitor family heavy chain-related protein) (IHRP) (Major acute phase protein) (MAP) - Sus scrofa (Pig), 921 aa. Q91W60 Inter alpha-trypsin inhibitor, heavy chain 4 - 1 . . . 930 625/958 (65%) 0.0 Mus musculus (Mouse), 941 aa. 1 . . . 941 743/958 (77%) O54882 PK-120 - Mus musculus (Mouse), 942 aa. 1 . . . 930 621/957 (64%) 0.0 1 . . . 942 740/957 (76%)

[0360] PFam analysis indicates that the NOV2a protein contains the domains shown in the Table 2F. TABLE 2F Domain Analysis of NOV2a Identities/ Similarities NOV2a for the Pfam Domain Match Region Matched Region Expect Value vwa 274 . . . 457 34/209 (16%) 1.1e−08 125/209 (60%) 

Example 3

[0361] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A. TABLE 3A NOV3 Sequence Analysis SEQ ID NO: 13          1365 bp NOV3a, ATGCTGCGGATCCTGTGCCTGGCACTCTGCAGCCTGCTGACTGGCACGCGAGCTGACCCTGGGG CG139008-01 DNA Sequence CACTGCTGCGGTTGGGCATGGACATCATGAACCGTGAGGTCCAGAGCGCCATGGATGAGAGTCA TATCCTGGAGAAGATGGCAGCCGAGGCAGGCAAGAAACAGCCAGGGATGAAACCTATCAAGGGC ATCACCAATTTGAAGGTGAAGGATGTCCAGCTGCCCGTCATCACACTGAACTTTGTACCTGGAG TGGGCATCTTCCAATGTGTGTCCACAGGCATGACCGTCACTGGCAAGAGCTTCATGGGAGGGAA CATGGAGATCATCGTGGCCCTGAACATCACAGCCACCAACCGGCTTCTGCGGGATGAGGAGACA GGCCTCCCCGTGTTCAAGAGTGAGGGCTGTGAGGTCATCCTGGTCAATGTGAAGACTAACCTGC CTAGCAACATGCTCCCCAAGATGGTCAACAAGTTCCTGGACAGCACCCTGCACAAAGTCCTCCC TGGGCTGATGTGTCCCGCCATCGATGCAGTCCTGGTGTATGTGAACAGGAAGTGGACCAACCTC AGTGACCCCATGCCTGTGGGCCAGATGGGCACCGTCAAATATGTTCTGATGTCCGCACCAGCCA CCACAGCCAGCTACATCCAACTGGACTTCAGTCCTGTGGTGCAGCAGCAAAAGGGCAAAACCAT CAAGCTTGCTGATGCCGGGGAGGCCCTCACGTTCCCTGAGGGTTATGCCAAAGGCTCGTCGCAG CTGCTGCTCCCAGCCACCTTCCTCTCTGCAGAGCTTGCCCTTCTGCAGAAGTCCTTTCATGTGA ATATCCACGATACAATGATTGGTGAGCTGCCCCCACAAACCACCAAGACCCTGGCTCGCTTCAT TCCTGAAGTGGCTGTAGCTTATCCCAAGTCAAAGCCCTTGACGACCCAGATCAAGATAAAGAAG CCTCCCAAGGTCACTATGAAGACAGGCAAGAGCCTGCTGCACCTCCACAGCACCCTGGAGATGT TCGCAGCTCGGTGGCGGAGCAAGGCTCCAATGTCCCTCTTTCTCCTAGAAGTGCACTTCAATCT GAAGGTCCAGTACTCAGTGCATGAGAACCAGCTGCAGATGGCCACTTCTTTGGACAGATTACTG AGCTTGTCCCGGAAGTCCTCATCGATTGGCAACTTCAATGAGAGGGAATTAACTGGCTTCATCA CCAGCTATCTCGAAGAAGCCTACATCCCAGTTGTCAATGATGTGCTTCAAGTGGGGCTCCCACT CCCGGACTTTCTGGCCATGAATTACAACCTGGCTGAGCTGGACATAGTAGAGCTTGGGGGCATC ATGGAACCTGCCGACATATGA ORF Start: ATG at 1                    ORF Stop: IGA at 1363 SEQ ID NO: 14           454 aa         MW at 49801.1 kD NOV3a, MLRILCLALCSLLTGTRADPGALLRLGMDIMNREVQSAMDESHILEKMAAEAGKKQPGMKPIKG CG139008-01 Protein Sequence ITNLKVKDVQLPVITLNFVPGVGIFQCVSTGMTVTGKSFMGGNMEIIVALNITATNRLLRDEET GLPVFKSEGCEVILVNVKTNLPSNMLPKMVNKFLDSTLHKVLPGLMCPAIDAVLVYVNRKWTNL SDPMPVGQMGTVKYVLMSAPATTASYIQLDFSPVVQQQKGKTIKLADAGEALTFPEGYAKGSSQ LLLPATFLSAELALLQKSFHVNIQDTMIGELPPQTTKTLARFIPEVAVAYPKSKPLTTQIKIKK PPKVTMKTGKSLLHLHSTLEMFAARWRSKAPMSLFLLEVHFNLKVQYSVHENQLQMATSLDRLL SLSRKSSSIGNFNERELTGFITSYLEEAYIPVVNDVLQVGLPLPDPLANNYNLAELDTVELGGI SEQ ID NO: 15          1374 bp NOV3b, AGATCTATGCTGCGGATCCTGTGCCTGGCACTCTGCAGCCTGCTGACTGGCACGCGAGCTGACC 233028732 DNA Sequence CTGGGGCACTGCTGCGGTTGGGCATGGACATCATGAACCGTGAGGTCCAGAGCGCCATGGATGA GAGTCATATCCTGGAGAAGATGGCAGCCGAGGCAGGCAAGAAACAGCCAGGGATGAAACCTATC AAGGGCATCACCAATTTGAACGTGAAGGATGTCCAGCTGCCCGTCATCACACTGAACTTTGTAC CTGGAGTGGGCATCTTCCAATGTGTGTCCACAGGCATGACCGTCACTGGCAAGAGCTTCATGGG AGGGAACATGGAGATCATCGTGGCCCTGAACATCACAGCCACCAACCGGCTTCTGCGGGATGAG GAGACAGGCCTCCCCGTGTTCAAGAGTGAGGGCTGTGAGGTCATCCTGGTCAATGTGAAGACTA ACCTGCCTAGCAACATGCTCCCCAAGATGGTCAACAAGTTCCTGGACAGCACCCTGCACAAAGT CCTCCCTGGGCTGATGTGTCCCGCCATCGATGCAGTCCTGGTGTATGTGAACAGGAAGTGGACC AACCTCAGTGACCCCATGCCTGTGGGCCAGATGGGCACCGTCAAATATGTTCTGATGTCCGCAC CAGCCACCACAGCCAGCTACATCCAACTGGACTTCAGTCCTGTGGTGCAGCAGCAAAAGGGCAA AACCATCAAGCTTGCTGATGCCGGGGAGGCCCTCACGTTCCCTGAGGGTTATGCCAAAGGCTCG TCGCAGCTGCTGCTCCCAGCCACCTTCCTCTCTGCAGAGCTTGCCCTTCTGCAGAAGTCCTTTC ATGTGAATATCCAGGATACAATGATTGGTGAGCTGCCCCCACAAACCACCAAGACCCTGGCTCG CTTCATTCCTGAAGTGGCTGTAGCTTATCCCAAGTCAAAGCCCTTGACGACCCAGATCAAGATA AAGAAGCCTCCCAAGGTCACTATGAAGACAGGCAAGAGCCTGCTGCACCTCCACAGCACCCTGG AGATGTTCGCAGCTCGGTGGCGGAGCAAGGCTCCAATGTCCCTCTTTCTCCTAGAAGTGCACTT CAATCTGAAGGTCCAGTACTCAGTGCATGAGAACCAGCTGCAGATGGCCACTTCTTTGGACAGA TTACTGAGCTTGTCCCGGAAGTCCTCATCGATTGGCAACTTCAATGAGAGGGAATTAACTGGCT TCATCACCAGCTATCTCGAAGAAGCCTACATCCCAGTTGTCAATGATGTGCTTCAAGTGGGGCT CCCACTCCCGGACTTTCTGGCCATGAATTACAACCTGGCTGAGCTGGACATAGTAGAGCTTGGG GGCATCATGGAACCTGCCGACATACTCGAG ORF Start: at 1                        ORF Stop: end of sequence SEQ ID NO: 16           458 aa         MW at 50286.7 kD NOV3b, RSMLRILCLALCSLLTGTRADPGALLRLGMDIMNREVQSAMDESHILEKMAAEAGKKQPGMKPI 233028732 Protein Sequence KGITNLKVKDVQLPVITLNFVPGVGIFQCVSTGMTVTGKSFMGGNMEIIVALNITATNRLLRDE ETGLPVFKSEGCEVILVNVKTNLPSNMLPKMVNKFLDSTLHKVLPGLMCPAIDAVLVYVNRKWT NLSDPMPVGQMGTVKYVLMSAPATTASYIQLDFSPVVQQQKGKTIKLADAGEALTFPEGYAKGS SQLLLPATFLSAELALLQKSFHVNIQDTMIGELPPQTTKTLARFIPEVAVAYPKSKPLTTQIKI KKPPKVTMKTGKSLLHLHSTLEMFAARWRSKAPMSLFLLEVHFNLKVQYSVHENQLQMATSLDR LLSLSRKSSSIGNFNERELTGFITSYLEEAYIPVVNDVLQVGLPLPDFLAMNYNLAELDIVELG GIMEPADILE SEQ ID NO: 17          1226 bp NOV3c, ATGCTGCGGATCCTGTGCCTGGCACTCTGCAGCCTGCTGACTGGCACGCGAGCTGACCCTGGGG CG139008-02 DNA Sequence CACTGCTGCGGTTGGGCATGGACATCATGAACCGTGAGGTCCAGAGCGCCATGGATGAGAGTCA TATCCTGGAGAAGATGGCAGCCGAGGCAGGCAAGAAACAGCCAGGGATGAAACCTATCAAGGGC ATCACCAATTTGAAGGTGAAGGATGTCCAGCTGCCCGTCATCACACTGAACTTTGTACCTGGAG TGGGCATCTTCCAATGTGTGTCCACAGGCATGACCGTCACTGGCAAGAGCTTCATGGGAGGGAA CATGGAGATCATCGTGGCCCTGAACATCACAGCCACCAACCGGCTTCTGCGGGATGAGGAGACA GGCCTCCCCGTGTTCAAGAGTGAGGGCTGTGAGGTCATCCTGGTCAATGTGAAGACTAACCTGC CTAGCAACATGCTCCCCAAGATGGTCAACAAGTTCCTGGACAGCACCCTGCACAAAGTCCTCCC TGGGCTGATGTGTCCCGCCATCGATGCAGTCCTGGTGTATGTGAACAGGAAGTGGACCAACCTC AGTGACCCCATGCCTGTGGGCCAGATGGGCACCGTCAAATATGTTCTGATGTCCGCACCAGCCA CCACAGCCAGCTACATCCAACTGGACTTCAGTCCTGTGGTGCAGCAGCAAAAGGGCAAAACCAT CAAGCTTGCTGATGCCGGGGAGGCCCTCACGTTCCCTGAGGGTTATGCCAAAGGCTCGTCGCAG CTGCTGCTCCCAGCCACCTTCCTCTCTGCAGAGCTTGCCCTTCTGCAGAAGTCCTTTCATGTGA ATATCCAGGATACAATGATTGGTGAGCTGCCCCCACAAACCACCAAGACCCTGGCTCGCTTCAT TCCTGAAGTGGCTGTAGCTTATCCCAAGTCAAAGCCCTTGACGACCCAGATCAAGATAAAGAAG CCTCCCAAGGTCACTATGAAGACAGGCAAGAGCCTGCTGCACCTCCACAGCACCCTGGAGATGT TCGCAGCTCGGTGGCGGAGCAAGGCTCCAATGTCCCTCTTTCTCCTAGAAGTGCACTTCAATCT GAAGGTCCAGTACTCAGTGCATGAGAACCAGCTGCAGATGGCCACTTCTTTGGACAGGAGAGGG AATTAA CTGGCTTCATCACCAGCTATCTCGAAGAGCCTACATCCCAGTTGTCAATGATGTGCTT TCAGTGGGCT ORF Start: ATG at 1                    ORF Stop: TAA at 1156 SEQ ID NO: 18           385 aa         MW at 42216.5 kD NOV3c, MLRILCLALCSLLTGTRADPGALLRLGMDIMNREVQSAMDESHILEKMAAEAGKKQPGMKPIKG CG139008-02 Protein Sequence ITNLKVKDVQLPVITLNFVPGVGIFQCVSTGMTVTGKSFMGGNNEIIVALNITATNRLLRDEET GLPVPKSEGCEVILVNVKTNLPSNMLPKMVNKFLDSTLHKVLPGLMCPAIDAVLVYVNRKWTNL GLPVFKSEGCEVILVNVKTNLPSNMLPKMVNKFLDSTLHKVLPGLMCPAIDAVLVYVNRKWTNL LLLPATFLSAELALLQKSFHVNIQDTMIGELPPQTTKTLARFIPEVAVAYPKSKPLTTQIKIKK PPRVTMKTGKSLLHLHSTLEMPAARWRSKAPMSLFLLEVHFNLKVQYSVHENQLQMATSLDRRG N

[0362] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B. TABLE 3B Comparison of NOV3a against NOV3b and NOV3c. Identities/ NOV3a Residues/ Similarities for the Protein Sequence Match Residues Matched Region NOV3b 1 . . . 454 454/454 (100%) 3 . . . 456 454/454 (100%) NOV3c 1 . . . 382 382/382 (100%) 1 . . . 382 382/382 (100%)

[0363] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C. TABLE 3C Protein Sequence Properties NOV3a SignalP Cleavage site between residues 19 and 20 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 3; pos. chg 1; neg. chg 0 H-region: length 13; peak value 9.26 PSG score: 4.86 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 4.69 possible cleavage site: between 18 and 19 >>> Seems to have a cleavable signal peptide (1 to 18) ALOM: Klein et al's method for TM region allocation Init position for calculation: 19 Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = −2.87 Transmembrane 169-185 PERIPHERAL Likelihood = 1.59 (at 255) ALOM score: −2.87 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 9 Charge difference: −2.0 C(0.0)-N(2.0) N >= C: N-terminal side will be inside >>> membrane topology: type 1a (cytoplasmic tail 186 to 454) MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 7.85 Hyd Moment(95): 8.62 G content: 1 D/E content: 1 S/T content: 3 Score: −2.21 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 27 TRA|DP NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 9.9% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: LRIL none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: too long tail Dileucine motif in the tail: found LL at 257 LL at 258 LL at 270 LL at 332 LL at 356 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 89 COIL: Lupas's algorithm to detect coiled-coil regions 27 M 0.73 28 D 0.73 29 I 0.73 30 M 0.73 31 N 0.73 32 R 0.73 33 E 0.73 34 V 0.73 35 Q 0.73 36 S 0.73 37 A 0.73 38 M 0.73 39 D 0.73 40 E 0.73 41 S 0.73 42 H 0.73 43 I 0.73 44 L 0.73 45 E 0.73 46 K 0.73 47 M 0.73 48 A 0.73 49 A 0.73 50 E 0.73 51 A 0.73 52 G 0.73 53 K 0.73 54 K 0.73 total: 28 residues Final Results (k = 9/23): 44.4%: endoplasmic reticulum 22.2%: Golgi 11.1%: plasma membrane 11.1%: vesicles of secretory system 11.1%: extracellular, including cell wall >> indication for CG139008-01 is end (k = 9)

[0364] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3D. TABLE 3D Geneseq Results for NOV3a NOV3a Residues/ Identities/ Geneseq Protein/Organism/Length [Patent #, Match Similarities for the Expect Identifier Date] Residues Matched Region Value AAM51697 Human new lipid binding protein 2 - 1 . . . 454 454/454 (100%) 0.0 Homo sapiens, 454 aa. 1 . . . 454 454/454 (100%) [WO200179493-A1, 25 OCT. 2001] AAB47337 FCTR14 - Homo sapiens, 454 aa. 1 . . . 454 454/454 (100%) 0.0 [WO200146231-A2, 28 JUN. 2001] 1 . . . 454 454/454 (100%) ABB08898 Human BPIL 325-3 SEQ ID NO 35 - 1 . . . 454 454/454 (100%) 0.0 Homo sapiens, 454 aa. 1 . . . 454 454/454 (100%) [WO200136478-A2, 25 MAY 2001] ABB08899 Human BPIL 325-4 SEQ ID NO 45 - 1 . . . 444 442/444 (99%)  0.0 Homo sapiens, 453 aa. 1 . . . 443 443/444 (99%)  [WO200136478-A2, 25 MAY 2001] ABG10878 Novel human diagnostic protein 1 . . . 454 441/455 (96%)  0.0 #10869 - Homo sapiens, 455 aa. 1 . . . 455 444/455 (96%)  [WO200175067-A2, 11 OCT. 2001]

[0365] In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3E. TABLE 3E Public BLASTP Results for NOV3a NOV3a Identities/ Protein Residues/ Similarities for Accession Match the Matched Expect Number Protein/Organism/Length Residues Portion Value CAC50178 Sequence 27 from Patent WO0146231 -  1 . . . 454  454/454 (100%) 0.0 Homo sapiens (Human), 454 aa.  1 . . . 454  454/454 (100%) Q8NFQ5 Bactericidal/permeability-increasing  1 . . . 444 442/444 (99%) 0.0 protein-like 3 - Homo sapiens (Human),  1 . . . 443 443/444 (99%) 453 aa. Q05704 Potential ligand-binding protein - Rattus 59 . . . 444 130/395 (32%) 3e−57 rattus (Black rat), 470 aa (fragment). 73 . . . 463 229/395 (57%) CAD12150 Sequence 3 from Patent WO0179269 - 59 . . . 444 125/394 (31%) 2e−52 Homo sapiens (Human), 637 aa. 241 . . . 630  222/394 (55%) CAC18887 DJ726C3.5 (ortholog of potential 59 . . . 444 125/394 (31%) 2e−52 ligand_binding protein RY2G5 (Rat)) - 73 . . . 462 222/394 (55%) Homo sapiens (Human), 469 aa (fragment).

[0366] PFam analysis indicates that the NOV3a protein contains the domains shown in the Table 3F. TABLE 3F Domain Analysis of NOV3a Identities/ NOV3a Similarities Match for the Pfam Domain Region Matched Region Expect Value LBP_BPI_CETP_C 291 . . . 429 41/140 (29%) 1.3e−11 95/140 (68%)

Example 4

[0367] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A. TABLE 4A NOV4 Sequence Analysis SEQ ID NO: 19               765 bp NOV4a, TCGCCCTTC ATGGTGATGTCCCAGGCCACCTACACGTTCCTCACGTGCTTCGCCGGCTTCTGCC CG145877-01 DNA Sequence TCATCTGGGGTCTCATCGTCCTGCTCTGCTGCTTCTGCAGCTTCCTGCGCCGCCGCCTCAAACG GCGCCAGGAGGAGCGACTGCGCGAGCAGAACCTGCGCGCCCTAGAGCTGGAGCCCCTCGAACTC GAGGGCAGTCTGGCCGGGAGCCCCCCGGGCCTGGCGCCGCCGCAGCCACCACCACACCGTAGCC GCCTGGAGGCGCCGGCTCACGCGCACTCGCATCCGCACGTGCACGTGCACCCGCCGCCTACGCA CCTGTCGGTCCCGCCACGGCCCTGGAGCTACCCGCGCCAAGCGGAATCGGACATGTCCAAACCA CCGTGTTACGAAGAGGCGGTGCTGATGGCAGAGCCGCCGCCGCCCTATAGCGAGGTGCTCACGG ACACGCGCGGCCTCTACCGCAAGATCGTCACGCCCTTCCTGAGTCGCCGCGACAGCGCGGAGAA GCAGGAGCAGCCGCCTCCCAGCTACAAGCCGCTCTTCCTGGACCGGGGCTACACCTCCGCGCTG CACCTGCCCAGCGCCCCTCGGCCCGCGCCGCCCTGCCCAGCCCTCTGCCTGCAGGCCGACCGTG GCCGCCGGGTCTTCCCCAGCTGGACCGACTCAGAGCTCAGCAGCCGCGAGCCCCTGGAGCACGG AGCTTGGCGTCTGCCGGTCTCCATCCCCTTGTTCGGGAGGACTACAGCCGTAT AGAGGGGC ORF Start: ATG at 10                       ORF Stop: TAG at 757 SEQ ID NO: 20               249 aa         MW at 28180.1 kD NOV4a, MVMSQATYTFLTCFAGFWLIWGLIVLLCCFCSFLRRRLKRRQEERLREQNLRALELEPLELEGS CG145877-01 Protein Sequence LAGSPPGLAPPQPPPHRSRLEAPAHAHSHPHVHVHPPPTHLSVPPRPWSYPRQAESDMSKPPCY EEAVLMAEPPPPYSEVLTDTRGLYRKIVTPFLSRRDSAEKQEQPPPSYKPLPLDRGYTSALHLP SAPRPAPPCPALCLQADRGRRVFPSWTDSELSSREPLEHGAWRLPVSIPLFGRTTAV

[0368] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B. TABLE 4B Protein Sequence Properties NOV4a SignalP Cleavage site between residues 35 and 36 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 0; pos. chg 0; neg. chg 0 H-region: length 34; peak value 11.41 PSG score: 7.01 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 0.65 possible cleavage site: between 31 and 32 >>> Seems to have a cleavable signal peptide (1 to 31) ALOM: Klein et al's method for TM region allocation Init position for calculation: 32 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) . . . fixed PERIPHERAL Likelihood = 8.33 (at 233) ALOM score: 8.33 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 15 Charge difference: 4.0 C(5.0)-N(1.0) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 5 Hyd Moment(75): 4.61 Hyd Moment(95): 3.22 G content: 2 D/E content: 1 S/T content: 5 Score: −0.42 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 51 RRQ|EE NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.6% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: nuclear Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 43.5%: mitochondrial 43.5%: nuclear 13.0%: extracellular, including cell wall >> indication for CG145877-01 is mit (k = 23)

[0369] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C. TABLE 4C Geneseq Results for NOV4a NOV4a Identities/ Residues/ Similarities for Geneseq Protein/Organism/Length Match the Matched Expect Identifier [Patent #, Date] Residues Region Value ABG08144 Novel human diagnostic protein #8135 - 12 . . . 77  35/66 (53%) 3e−10 Homo sapiens, 436 aa. 312 . . . 376  38/66 (57%) [WO200175067-A2, 11 OCT. 2001] ABG27250 Novel human diagnostic protein 65 . . . 202 43/140 (30%)  4e−06 #27241 - Homo sapiens, 406 aa. 23 . . . 150 54/140 (37%)  [WO200175067-A2, 11 OCT. 2001] AAG67355 Amino acid sequence of a rat N-WASP 66 . . . 140 32/80 (40%) 1e−05 protein - Rattus rattus, 501 aa. 294 . . . 373  36/80 (45%) [WO200144292-A2, 21 JUN. 2001] AAM52319 Rat N-WASP protein - Rattus rattus, 66 . . . 140 32/80 (40%) 1e−05 501 aa. [WO200171356-A2, 294 . . . 373  36/80 (45%) 27 SEP. 2001] AAW46890 Rat Neural-Wiskott-Aldrich syndrome 66 . . . 140 32/80 (40%) 1e−05 protein - Rattus sp, 501 aa. 294 . . . 373  36/80 (45%) [JP10072494-A, 17 MAR. 1998]

[0370] In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D. TABLE 4D Public BLASTP Results for NOV4a NOV4a Identities/ Protein Residues/ Similarities for Accession Match the Matched Expect Number Protein/Organism/Length Residues Portion Value Q9BTA7 Hypothetical protein - Homo sapiens 1 . . . 249 245/253 (96%) e−147 (Human), 253 aa. 1 . . . 253 246/253 (96%) Q8TB68 Hypothetical protein MGC10772 - 1 . . . 249 248/274 (90%) e−146 Homo sapiens (Human), 274 aa. 1 . . . 274 248/274 (90%) Q8WU53 Similar to hypothetical protein 1 . . . 249 247/274 (90%) e−145 MGC10772 - Homo sapiens (Human), 1 . . . 274 247/274 (90%) 274 aa. P13983 Extensin precursor (Cell wall 69 . . . 202   38/134 (28%) 2e−06  hydroxyproline-rich glycoprotein) - 302 . . . 414   49/134 (36%) Nicotiana tabacum (Common tobacco), 620 aa. Q94ES6 Nodule extensin - Pisum sativum 64 . . . 203   40/144 (27%) 7e−06  (Garden pea), 181 aa. 31 . . . 169   53/144 (36%)

Example 5

[0371] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A. TABLE 5A NOV5 Sequence Analysis SEQ ID NO: 21              1126 bp NOV5a, GGCACGAGGCCCGCGCGCGGGGGCGCCCAGGCCACTGGGCTCCGCGGAGCCAGCGAGAGGTCTG CG151161-02 DNA Sequence CGCGGAGTCTGAGCCGCGCTCGTCCCGTCCCAAGGCCGACGCCAGCACGCCGTC ATGGCCCCCG CAGCCGCGACCGGGGGCAGCACCCTGCCCAGTGGCTTCTCGGTCTTCACCACCTTGCCCGACTT GCTCTTCATCTTTGAGTTTATCTTCGGGGGCCTGGTGTGGATCCTGGTGGCCTCCTCCCTGGTG CCCTGGCCCCTGGTCCACGGCTGGGTGATGTTCGTGTCTGTGTTCTGCTTCGTGGCCACCACCA CCTTGATCATCCTGTACATAATTGGAGCCCACGGTGGAGAGACTTCCTGCGTCACCTTGGACGC AGCCTACCACTGCACCGCTGCCCTCTTTTACCTCAGCGCCTCAGTCCTGGAGGCCCTGGCCACC ATCACGATGCAAGACGGCTTCACCTACAGGCACTACCATGAAAACATTGCTGCCGTGGTGTTCT CCTACATAGCCACTCTGCTCTACGTGGTCCATGCGGTGTTCTCTTTAATCAGATCGAAGTCTTC ATAA AGCCGCAGTAGAACTTGAGCTGAAAACCCAGATGGTGTTAACTGGCCGCCCCACTTTCCG GCATAACTTTTTAGAAACAGAAATGCCCTTGATGGTGGAAAAAAAGAAAACAACCACCCCCCCA CTGCCCAAAAAAAAAAGCCCTGCCCTGTTGCTCGTGGGTGCTGTGTTTACTCTCCCGTGTGCCT TCGCGTCCGCGTTGCGAGCTTGCTGTGTCTAACCTCCAACTGCTGTGCTGTCTGCTAGGGTCAC CTCCTGTTTGTGAAAGGGGACCTTCTTGTTCGGGGGTGGGAAGTGGCGACCGTGACCTGAGAAG GAAAGAAAGATCCTCTGCTCACCCCTCGAGCAGCTCTCGAGAACTACCTGTTGGTATTGTCCAC AAGCTCTCCCGAGCGCCCCATCTTGTGCCATGTTTTAAGTCTTCATGGATGTTCTGCATGTCAT GGGGACTAAAACTCACCCAACAGATCTTTCCAGAGGTCCATGGTGGAAGACGATAACCCTGTGA AATACTTTATAAAATGTCTTAATGTTCAAAAAAAAAAA ORF Start: ATG at 119                      ORF Stop: TAA at 578 SEQ ID NO: 22               153 aa         MW at 16713.3 kD NOV5a, MAPAAATGGSTLPSGFSVFTTLPDLLFIFEFIFGGLVWILVASSLVPWPLVQGWVNFVSVFCFV CG151161-02 Protein Sequence ATTTLIILYIIGAHGGETSWVTLDAAYHCTAALFYLSASVLEALATITMQDGFTYRHYHENIAA VVFSYIATLLYVVHAVFSLIRWKSS SEQ ID NO: 23               464 bp NOV5b, GGCACGAGGCCCGCGCGCGGGGGCGCCCAGGCCACTGGGCTCCGCGGAGCCAGCGAGAGGTCTG CG151161-01 DNA Sequence CGCGGAGTCTGAGCCGCCCTCGTCCCGTCCCAAGGCCGACGCCAGCACGCCGTC ATGGCCCCCG CAGCGGCGACGGGGGGCAGCACCCTCCCCAGTGGCTTCTCGGTCTTCACCACCTTGCCCGACTT GCTCTTCATCTTTGAGTTTGACGCAACCTACCACTGCACCGCTGCCCTCTTTTACCTCAGCGCC TCAGTCCTGGAGGCCCTGGCCACCATCACGATGCAAGACGGCTTCACCTACAGGCACTACCATG AAAACATTGCTGCCGTGGTGTTCTCCTACATAGCCACTCTGCTCTACGTCGTCCATGCGGTGTT CTCTTTAATCAGATGGAAGTCTTCATAA AGCCGCAGTAGAACTTGAGCTGAAAACCCAGATGGT GTTAACTGGCCGCCCC ORF Start: ATG at 119                      ORF Stop: TAA at 410 SEQ ID NO: 24                97 aa         MW at 10651.1 kD NOV5b, MAPAAATCGSTLPSGFSVFTTLPDLLFIFEFDATYHCTAALFYLSASVLEALATITMQDGFTYR CG151161-01 Protein Sequence HYHENIAAVVPSYIATLLYVVHAVFSLIRWKSS

[0372] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 5B. TABLE 5B Comparison of NOV5a against NOV5b. Identities/ NOV5a Residues/ Similarities for the Protein Sequence Match Residues Matched Region NOV5b 1 . . . 153 94/153 (61%) 1 . . . 97  94/153 (61%)

[0373] Further analysis of the NOV5a protein yielded the following properties shown in Table 5C. TABLE 5C Protein Sequence Properties NOV5a SignalP Cleavage site between residues 67 and 68 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 0; pos. chg 0; neg. chg 0 H-region: length 23; peak value 8.79 PSG score: 4.39 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −1.89 possible cleavage site: between 53 and 54 >>> Seems to have a cleavable signal peptide (1 to 53) ALOM: Klein et al's method for TM region allocation Init position for calculation: 54 Tentative number of TMS(s) for the threshold 0.5: 3 INTEGRAL Likelihood = −7.64 Transmembrane 55-71 INTEGRAL Likelihood = −0.90 Transmembrane  95-111 INTEGRAL Likelihood = −4.30 Transmembrane 129-145 PERIPHERAL Likelihood = 10.08 (at 74) ALOM score: −7.64 (number of TMSs: 3) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 26 Charge difference: 0.0 C(−1.0)-N(−1.0) N >= C: N-terminal side will be inside >>> membrane topology: type 3a MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 2.25 Hyd Moment(95): 2.24 G content: 3 D/E content: 1 S/T content: 7 Score: −5.30 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 2.0% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: KKXX-like motif in the C-terminus: RWKS SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 66.7%: endoplasmic reticulum 33.3%: mitochondrial >> indication for CG151161-02 is end (k = 9)

[0374] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5D. TABLE 5D Geneseq Results for NOV5a NOV5a Identities/ Geneseq Protein/Organism/Length [Patent #, Match the Matched Expect Identifier Date] Residues Region Value ABB50292 T cell differentiation protein Mal 1 . . . 153  153/153 (100%) 5e−85 ovarian tumour marker protein, #74 - 1 . . . 153  153/153 (100%) Homo sapiens, 153 aa. [WO200175177-A2, 11 OCT. 2001] AAP80929 Sequence of human T-cell protein 1 . . . 153 150/153 (98%) 3e−82 designated MAL - Homo sapiens, 153 1 . . . 153 151/153 (98%) aa. [WO8807549-A, 06 OCT. 1988] AAP81879 Sequence of full-length human T-cell 1 . . . 153 150/153 (98%) 3e−82 protein derived from mature T cells - 1 . . . 153 151/153 (98%) Homo sapiens, 153 aa. [WO8807549-A, 06 OCT. 1988] AAU85517 Clone #18966 of lung tumour protein - 3 . . . 143  60/141 (42%) 8e−28 Homo sapiens, 148 aa. 2 . . . 142  91/141 (63%) [WO200204514-A2, 17 JAN. 2002] AAB76862 Human lung tumour protein related 3 . . . 143  60/141 (42%) 8e−28 protein sequence SEQ ID NO: 338 - 2 . . . 142  91/141 (63%) Homo sapiens, 148 aa. [WO200100828-A2, 04 JAN. 2001]

[0375] In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5E. TABLE 5E Public BLASTP Results for NOV5a NOV5a Identities/ Protein Residues/ Similarities for Accession Match the Matched Expect Number Protein/Organism/Length Residues Portion Value P21145 Myelin and lymphocyte protein 1 . . . 153  153/153 (100%) 1e−84 (T-lymphocyte maturation-associated 1 . . . 153  153/153 (100%) protein) - Homo sapiens (Human), 153 aa. Q64349 Myelin and lymphocyte protein 1 . . . 153 136/153 (88%) 2e−77 (T-lymphocyte maturation-associated 1 . . . 153 147/153 (95%) protein) (17 kDa myelin vesicular protein) (MVP17) (NS 3) - Rattus norvegicus (Rat), 153 aa. O09198 Myelin and lymphocyte protein 1 . . . 153 133/153 (86%) 2e−75 (T-lymphocyte maturation-associated 1 . . . 153 145/153 (93%) protein) - Mus musculus (Mouse), 153 aa. Q28296 Myelin and lymphocyte protein 1 . . . 153 135/153 (88%) 2e−75 (T-lymphocyte maturation-associated 1 . . . 153 146/153 (95%) protein) (VIP17 proteolipid) - Canis familiaris (Dog), 153 aa. Q9D2R2 Myelin and lymphocyte protein; T-cell 1 . . . 153  84/153 (54%) 4e−34 differentiation protein - Mus musculus 1 . . . 97   91/153 (58%) (Mouse), 97 aa.

Example 6

[0376] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A. TABLE 6A NOV6 Sequence Analysis SEQ ID NO: 25              4801 bp NOV6a, CCGCTGCGGGCTCGGGCGCCGCAGCGCGCCGGCCCGAGCCCCTGGACGAGGCCCACGGAGCCGC CG155653-01 DNA Sequence TCGCCCCGACCCAGCCGCCCGATGTCCTCAAAATGGAGGCAGCGCGGGCGGCGGCGTGAAGAAA GCGGCGCTGTGGGCGCGGGAGTAGGGGCCCGGGCGGAGGCGGTGGCGGG ATGGGGCTGCTGCTC ATGATCCTGGCGTCGGCCGTGCTGGGTTCCTTCCTCACGCTCCTCGCCCAGTTCTTCCTGCTGT ACCGCAGACAGCCCCAGCCGCCGGCGGACGAGGCCGCCCGCGCGCGCGAGGGCTTCCGCTACAT CAAGCCAGTGCCGGGCCTGCTCCTAAGGGAGTACCTTTATGGCGGCGGCCGGGATGAGGAGCCC TCCGGAGCGGCCCCTGAGGGCGGCGCGACCCCCACCGCGGCCCCCGAGACCCCCGCCCCGCCGA CGCGGGAGACTTGCTACTTCCTCAACGCCACCATCCTATTCCTGTTCCGGGAGTTGCGGGACAC CGCGCTGACCCGCCGCTGGGTCACCAAGAAGATCAAGGTGGAGTTCGAGGAGCTGCTGCAGACC AAGACGGCCCGGCGCCTGCTGGACGCGCTGAGCCTGCGGGACGTGTTCCTGGGCGAGACGGTGC CCTTCATCAAGACCATCCGGCTCGTGCGGCCAGTCGTGCCCTCGGCCACCGGGGAGCCCGATGG CCCTGAAGGGGACGCGCTGCCCGCCGCCTGCCCCGAGGAGCTCGCCTTCGAGGCGGAGGTGGAG TACAACCGGGGCTTCCACCTCGCCATCGACGTGGACCTGGTCTTCGGCAAGTCCGCCTACTTGT TTGTCAAGCTGTCCCGCGTGGTGGGAAGGCTGCGCTTGGTCTTTACGCGCGTGCCCTTCACCCA CTGGTTCTTCTCCTTCGTGGAAGACCCGCTGATCGACTTCGAGGTGCGCTCCCAGTTTGAAGGG CGGCCCATGCCCCAGCTCACCTCCATCATCGTCAACCAGCTCAAGAAGATCATCAAGCGCAAGC ACACCCTACCGAATTACAAGATCAGGTTTAAGCCGTTTTTTCCATACCAGACCTTGCAAGGATT TGAAGAAGATGAAGAGCATATCCATATACAACAATGGGCACTTACTGAAGGCCGTCTTAAAGTT ACGTTGTTAGAATGTAGCAGGTTACTCATTTTTGGATCCTATGACAGAGAGGCAAATGTTCATT GCACACTTGAGTTAAGCAGTAGTGTTTGCGAAGAAAAACAGAGGAGTTCTATTAAGACGGTTGA ATTAATAAAAGGAAATTTACAAAGTGTTGGACTTACACTTCGTCTTGTCCAGTCAACTCATGCG TATGCTGGGCACGTCATCATTGAAACTGTGGCTCCAAACTCGCCTGCTGCAATTGCAGATCTTC AGCGGGGAGATCGACTTATCGCCATTGGAGGTGTGAAAATCACATCAACACTGCAAGTGTTGAA GCTTATCAAGCACGCTGGTGACCGAGTCCTGGTGTACTATGAAACGCCTGTTGGCCAGAGTAAT CAAGGTGCAGTGCTGCAAGATAACTTTGGCCAGTTGGAAGAAAACTTTTTGTCAAGCTCATGCC AATCGGGTTATGAAGAGGAAGCTGCCGGGTTGACAGTAGATACTGAAAGTAGAGAGCTGGATTC TGAATTTGAAGACTTCGCAAGTGATGTCAGAGCACAAAATGACTTCAAACATGAGGCACAATCA TTAAGTCATAGTCCCAAACGTGTTCCAACAACACTTTCTATTAAACCCCTTGGAGCTATATCAC CAGTTTTAAACCGTAAATTAGCTGTAGGAACTCACCCACTACCACCGAAAATTCAGTCCAAAGA TGGAAATAAACCTCCACCCCTAAAAACTTCTGAGATAACAGACCCAGCACAAGTGTCAAAACCA ACCCAAGGATCTGCTTTCAAACCACCTCTGCCACCACGACCACAAGCGAAAGTTCCTTTGCCTT CCGCCGATGCTCCAAATCAGGCCAGAACCAGATGTTCTCGTTGAAAGCCAGAGAAGGTGGTGCC ACCTCCTCTTGTAGATAAATCTGCTGAAAAGCAAGCAAAAAATGTGGATGCCATAGACGATGCA GCTGCACCTAAGCAATTTTTAGCAAAGCAAGAAGTGGCCAAAGATGTCACTTCAGAAACTTCCT GCCCTACTAAGGACAGTTCGGACGACCGTCAAACATGGGAATCATCAGAAATTCTTTATCCTAA TAAGCTAGGAAAATCGACAAGAACCAGAGCATCCTGTTTGTTTGACATAGAAGCCTGTCACAGG TACTTAAACATTGCATTGTGCTGCACGGATCCTTTCAAGTTGGGAGGTCTCATCTGTTTGCGGC ATGTTAGTTTAAAACTTGAAGATGTGGCTTTAGGATGCCTAGCTACATCAAACACGGAATACCT TTCCAAATTGAGACTGGAAGCCCCCTCACCTAACGCTATAGTCACTAGAACCGCACTACGCAAT CTGAGTATGCAAAAGGATTCAATGACAAATTTTGCTATGGTGACATTACTATTCACTTCAAAAT ATTTGAAAGAAGGAGAATCAGACCACCATGTAGTTACTAACGTAGAAAAAGAAAAAGAACCCCA TTTGGTTGAAGAAGTTTCTGTTCTCCCTAAAGAGGAGCAATTTGTTGGACAGATGGGTTTAACA GAAAACAAACACAGTTTTCAGGATACTCAGTTCCAGAACCCAACATCGTGTGACTACTGTAAGA AAAAAGTTTGGACTAAAGCAGCTTCCCAGTGTATGTTTTGTGCTTATGTTTGCCATAAAAAATG TCAAGAAAAGTGTCTAGCTGAGACTTCTGTTTGTGGAGCAACTGATAGGCGAATAGACAGGACA CTGAAAAACCTTAGGCTGGAAGGACAGGAAACCCTCTTAGGCCTGCCTCCTCGTGTTGATGCTG AAGCTAGCAAGTCAGTCAATAAAACAACAGGTTTGACAACGCATATTATCAATACTAGTTCTCG TTTATTAAATTTGCGTCAAGTCTCTAAAACTCGCCTTTCTGAACCAGGAACCGATCTCGTAGAA CCTTCACCAAAACACACACCCAACACGTCAGACAACGAAGGCAGTGACACGGAGGTCTGTGGTC CAAACAGTCCTTCTAAACGGGGAAACAGCACAGGAATAAAGTTAGTGAGAAAAGAGGGTGGTCT GGATGACAGTGTTTTCATTGCAGTTAAAGAAATTGGTCGTGATCTGTACAGGGGCTTGCCTACA GAGGAAAGGATCCAGAAACTAGAGTTCATGTTGGATAAGCTACAGAATGAAATTGATCAGGAGT TGGAACACAATAATTCCCTTGTTAGAGAAGAAAAAGAGACAACTGATACAAGGAAAAAATCACT TCTTTCTGCTGCCTTAGCTAAATCAGGTGAAAGGCTACAAGCTCTAACACTTCTTATGATTCAC TACAGAGCAGGCATTGAAGATATAGAAACTTTAGAAAGTCTGTCTTTAGACCAGCACTCCAAAA AAATAAGCAAGTACACAGATGATACAGAAGAAGACCTTGATAATGAAATAAGCCAACTAATAGA CTCTCAGCCATTCAGCAGCATATCAGATGACTTATTTGGCCCATCCGAGTCTGTGTAG CAGACA GGTCTATTTAAACTTTCAAATGAACAGGGTAAAGTTCCATCTAAAGTACCACAGATACAACCAT GTTTAAATCCTCGTATGCACTCTGGCCTGCTTCTCCAGTTACTTGCTTGTGTAAGAACAAAAAT GACAAAGGTTGTTTTCCAGTAAAAACATGACCAGCTTACTAATTGGTTGTTTTGGATTGCATTT ATAGCTATGCTTTTTTGGGTTTATACTGGGAATTTATTTTTACTAAATTATTTAACTTTTCTAA TTATGTAATTATGTAAGCTAGCTTTTCATGTTTATGTATGTATGGTGTCCCCTTGTGTTATTTT TCTTCCTCTTGGTTTTTGAATTAGTGTTAAATAGAATACTGTCTGGATTCTTAAAATATTTTCA TTTCCATCATGGTTATAACAAATTTGCTGCATCCCCAAACTGACAACAGCAATCACTGAGGGAA CAGGTTTTGAATCTTTCTTTTGTGTTATGAAGTTTATCGTCTCTACTTGCTTGAGATTTTTGTT ATTTTGGGGGTTTGGGGGTGCTTTTTGTTTTGTTTTTGCCAAATGTAACATGAAAGCAGATGCT GCAGCTTTAGTCTGTTATGCTGATTTACTAAAAAAAAATTTTTTACATATATTGCTTGCTTTCG ATCCTTCTGTGAAATTTTTTTCTAAAGCTTTTGTGCAGCTGTATCGTAAAAATATGGTGATTAA TTTGAAGAGCTTACATTGAAAGACAATGTAATAGGAAATAAATGTAGATTGCAGTTGGTCAAGA ATTTTGTAGAGAGGATAACAAGACTTAATTACTGAAAAACAGTAACATAGCATTTTGAAATATG ATCTTTTAAAATATTGATGCTTTCCTTTTAAATGGAAATTTAAATTTTATAATTAAAAGTTTAA ACATTTATGATAATTTTCCTCATCAGTTCTCCCATAGGAAATAAAGCATGTGAAAGGGTATTTA AAGTTTTGGAGGACTCTTTTTAAAATGACTGTGTTGATAACTAGTTTCCGCTCGTTTTGTTTTA GAAAAAACATTTTCATGTAGGAGTATTCTGTGAAGGAAAGGAATCATGCAAAATATACTTTTTG CTTTGGCGTCTTACAGTTGTAAAGGAATGGTGATCATTCTGAATACTTCTGTAGTGAGTATTCA T ORF Start: ATG at 178                      ORF Stop: TAG at 3640 SEQ ID NO: 26              1154 aa         MW at 128561.7 kD NOV6a, MGLLLMILASAVLGSFLTLLAQFFLLYRRQPEPPADEAARAGEGFRYIKPVPGLLLREYLYGGG CG155653-01 Protein Sequence RDEEPSGAAPEGGATPTAAPETPAPPTRETCYFLNATILFLFRELRDTALTRRWVTKKIKVEFE ELLQTKTAGRLLEGLSLRDVFLGETVPFIKTIRLVRPVVPSATGEPDGPEGEALPAACPEELAF EAEVEYNCGFHLATDVDLVFGKSAYLFVKLSRVVGRLRLVFTRVPFTHWFFSFVEDPLTDFEVR SQFEQRPMPQLTSIIVNQLKKIIKRKHTLPNYKIRFKPFFPYQTLQGFEEDEEHIMIQQWALTE GRLKVTLLECSRLLIFGSYDREANVHCTLELSSSVWEEKQRSSIKTVELIKGNLQSVGLTLRLV QSTDGYAGHVIIETVAPNSPAAIADLQRGDRLIAIGGVKITSTLQVLKLIKQAGDRVLVYYERP VGQSNQGAVLQDNFGGLEENFLSSSCQSGYEEEAAGLTVDTESRELDSEFEDLASDVRAQNEFK DEAQSLSHSPKRVPTTLSIKPLGAISPVLHRKLAVGSHPLPPKIQSKDGNKPPPLKTSEITDPA QVSKPTQGSAFKPPVPPRPQAKVPLPSADAPNQAEPDVLVEKPEKVVPPPLVDKSAEKQAKNVD AIDDAAAPKQFLAKQEVAKDVTSETSCPTKDSSDDRQTWESSEILYRNKLGKWTRTRASCLFDI EACHRYLNIALWCRDPFKLGGLICLGHVSLKLEDVAGCIIATSNTEYLSKLRLEAPSPKAIVTR TALRNLSMQKGFNDKFCYGDITIHFKYLKEGESDHHVVTNVEKEKEPHLVEEVSVLPKEEQFVG QMCLTENKHSFQDTQFQNPTWCDYCKKKVWTKAASQCMFCAYVCHKKCQEKCLAETSVCGATDR RIDRTLKNLRLEGQETLLGLPPRVDAEASKSVNKTTGLTRHTINTSSRLLNLRQVSKTRLSEPG TDLVEPSPKHTPNTSDNEGSDTEVCGPNSPSKRGNSTGIKLVRKEGGLDDSVFIAVKEIGRDLY RGLPTEERIQKLEFMLDKLQNEIDQELEHNNSLVREEKETTDTRKKSLLSAALAKSGERLQALT LLMIHYRAGIEDIETLESLSLDQHSKKISKYTDDTEEDLDNEISQLIDSQPFSSISDDLFGPSE SV

[0377] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B. TABLE 6B Protein Sequence Properties NOV6a SignalP Cleavage site between residues 22 and 23 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 0; pos. chg 0; neg. chg 0 H-region: length 27; peak value 11.55 PSG score: 7.15 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 0.74 possible cleavage site: between 14 and 15 >>> Seems to have a cleavable signal peptide (1 to 14) ALOM: Klein et al's method for TM region allocation Init position for calculation: 15 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) . . . fixed PERIPHERAL Likelihood = 1.38 (at 204) ALOM score: 1.38 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 7 Charge difference: −1.0 C(0.0)-N(1.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 1.54 Hyd Moment(95): 1.27 G content: 2 D/E content: 1 S/T content: 3 Score: −4.42 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 39 RRQ|PE NUCDISC: discrimination of nuclear localization signals pat4: KRKH (3) at 280 pat7: none bipartite: none content of basic residues: 12.5% NLS Score: −0.29 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: found TLPN at 284 RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: nuclear Reliability: 55.5 COIL: Lupas's algorithm to detect coiled-coil regions 1028 T 1.00 1029 E 1.00 1030 E 1.00 1031 R 1.00 1032 I 1.00 1033 Q 1.00 1034 K 1.00 1035 L 1.00 1036 E 1.00 1037 F 1.00 1038 M 1.00 1039 L 1.00 1040 D 1.00 1041 K 1.00 1042 L 1.00 1043 Q 1.00 1044 N 1.00 1045 E 1.00 1046 I 1.00 1047 D 1.00 1048 Q 1.00 1049 E 1.00 1050 L 1.00 1051 E 1.00 1052 H 1.00 1053 N 1.00 1054 N 1.00 1055 S 1.00 1056 L 1.00 1057 V 0.99 1058 R 0.99 1059 E 0.99 1060 E 0.94 1061 K 0.94 1062 E 0.94 1063 T 0.83 1064 T 0.83 1065 D 0.83 1066 T 0.83 1067 R 0.67 1068 K 0.67 1069 K 0.67 1070 S 0.67 1071 L 0.67 1072 L 0.67 1073 S 0.67 1074 A 0.67 1075 A 0.67 total: 48 residues Final Results (k = 9/23): 33.3%: extracellular, including cell wall 33.3%: nuclear 22.2%: mitochondrial 11.1%: cytoplasmic >> indication for CG155653-01 is exc (k = 9)

[0378] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6C. TABLE 6C Geneseq Results for NOV6a NOV6a Residues/ Identities/ Geneseq Protein/Organism/Length [Patent #, Match Similarities for the Expect Identifier Date] Residues Matched Region Value AAM78475 Human protein SEQ ID NO 1137 - 1 . . . 1154 1154/1204 (95%)  0.0 Homo sapiens, 1204 aa. 1 . . . 1204 1154/1204 (95%)  [WO200157190-A2, 09 AUG. 2001] AAU99614 Human glioma antigen KU-GB-5 - 264 . . . 1154  890/891 (99%) 0.0 Homo sapiens, 891 aa. 1 . . . 891  890/891 (99%) [WO200255695-A1, 18 JUL. 2002] ABG39902 Human peptide encoded by 436 . . . 1147  711/712 (99%) 0.0 SEQ ID 29567 - Homo sapiens, 712 1 . . . 712  712/712 (99%) aa. [WO200186003-A2, 15 NOV. 2001] AAM18088 Peptide #4522 encoded by probe for 436 . . . 1147  711/712 (99%) 0.0 measuring cervical gene expression - 1 . . . 712  712/712 (99%) Homo sapiens, 712 aa. [WO200157278-A2, 09 AUG. 2001] AAM70260 Human bone marrow expressed probe 436 . . . 1147  711/712 (99%) 0.0 encoded protein SEQ ID NO: 30566 - 1 . . . 712  712/712 (99%) Homo sapiens, 712 aa. [WO200157276-A2, 09 AUG. 2001]

[0379] In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D. TABLE 6D Public BLASTP Results for NOV6a NOV6a Protein Residues/ Identities/ Accession Match Similarities for the Expect Number Protein/Organism/Length Residues Matched Portion Value Q8NEN9 Similar to PDZ domain proteins -  1 . . . 1154 1154/1154 (100%)  0.0 Homo sapiens (Human), 1154 aa.  1 . . . 1154 1154/1154 (100%)  Q9UFF1 Hypothetical protein - Homo 642 . . . 1154  512/513 (99%) 0.0 sapiens (Human), 513 aa 1 . . . 513 512/513 (99%) (fragment). Q9VYR9 CG10362 protein (LD34222p) - 3 . . . 494 148/506 (29%) 2e−46 Drosophila melanogaster (Fruit 8 . . . 473 242/506 (47%) fly), 1037 aa. T20180 hypothetical protein C53B4.4a - 93 . . . 447  112/387 (28%) 4e−42 Caenorhabditis elegans, 1584 aa. 203 . . . 585  194/387 (49%) Q9U3L2 C53B4.4c protein - Caenorhabditis 93 . . . 447  112/387 (28%) 4e−42 elegans, 1449 aa. 68 . . . 450  194/387 (49%)

[0380] PFam analysis indicates that the NOV6a protein contains the domains shown in the Table 6E. TABLE 6E Domain Analysis of NOV6a Identities/ Similarities NOV6a for the Pfam Domain Match Region Matched Region Expect Value PDZ 366 . . . 448 19/88 (22%) 7.7e−10 62/88 (70%) DAG_PE-bind 841 . . . 888 18/51 (35%) 2.6e−09 36/51 (71%)

Example 7

[0381] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A. TABLE 7A NOV7 Sequence Analysis SEQ ID NO: 27              1157 bp NOV7a, CTTCGGCCTGTCGGTTTTCACC ATGGAGCAGCTGAGCTCAGCAAACACCCGCTTCGCCTTGGAC CG160093-01 DNA Sequence GTGTTCCTGGCGTTGAGTGAGAACAATCCGGCTGGAAACATCTTCATCTCTCCCTTCAGCATTT CATCTGCTATGGCCATGGTTTTTCTGGGGACCAGAGGTAACACGGCAGCACAGCTGTCCAAGAC TTTCCATTTCAACACGGTTGAAGAGGTTCATTCAAGATTCCAGAGTCTGAATGCTGATATCAAC AAACGTGGAGCGTCTTATATTCTGAAACTTGCTAATAGATTATATGGAGAGAAAACTTACAATT TCCTTCCTGAGTTCTGGGTTTCGACTCAGAAAACATATGGTGCTGACCTGGCCAGTGTGGATTT TCAGCATGCCTCTGAAGATGCAAGGAAGACCATAAACCAGTGGGTTGATAACATGACCAAACTT GTGCTAGTAAATGCCATCTATTTCAAGGGAAACTGGAAGGATAAATTCATGAAAGAAGCCACGA CGAATGCACCATTCAGATTGAATAAGAAAGACAGAAAAACTGTGAAAATGATGTATCAGAAGAA AAAATTTGCATATGGCTACATCGAGGACCTTAAGTGCCGTGTGCTGGAACTGCCTTACCAAGGC GAGGAGCTCAGCATGGTCATCCTGCTGCCGGATGACATTGAGGACGAGTCCACGGGCCTGAAGA AGATTGAGGAACAGTTGACTTTGGAAAAGTTGCATGAGTGGACTAAACCTGAGAATCTCGATTT CATTGAAGTTAATGTCAGCTTGCCCAGGTTCAAACTGGAAGAGAGTTACACTCTCAACTCCGAC CTCGCCCGCCTAGGTGTGCAGGATCTCTTTAACAGTAGCAAGGCTGATCTGTCTGGCATGTCAG GAGCCAGAGATATTTTTATATCAAAAATTGTCCACAAGTCATTTGTGGAAGTGAATGAAGAGGG AACAGAGGCGGCAGCTGCCACAGCAGGCATCGCAACTTTCTGCATGTTGATGCCCGAAGAAAAT TTCACTGCCGACCATCCATTCCTTTTCTTTATTCGGCATAATTCCTCAGGTAGCATCCTATTCT TGGGGAGATTTTCTTCCCCTAG AAGAAAGAGACTGTAGCAATACAAAAAATCAAGCTTAGTGCT AAGGG ORF Start: ATG at 23                       ORF Stop: TAG at 1109 SEQ ID NO: 28               362 aa         MW at 41001.3 kD NOV7a, MEQLSSANTRFALDLBLALSENNPAGNIFISPFSISSAMANVFLGTRGNTAAQLSKTFHFNTVE CG160093-01 Protein Sequence EVHSRFQSLNADINKRGASYILKLANRLYGEKTYNFLPEFLVSTQKTYGADLASVDFQHASEDA RKTINQWVDNMTKLVLVNAIYFKGNWKDKFMKEATTNAPFRLNKKDRKTVKMMYQKKKFAYGYI EDLKCRVLELPYQGEELSMVILLPDDIEDESTGLKKIEEQLTLEKLHEWTKPENLDFIEVNVSL PRFKLEESYTLNSDLARLGVQDLPNSSKADLSGMSGARDIFISKIVHKSFVEVNEEGTEAAAAT AGIATFCMLMPEENFTADHPFLFFIRHNSSCSILFLGRFSSP SEQ ID NO: 29              1550 bp NOV7b, CGGCGGCCTGTCGGAGCTGTTTGTGACGGTTTCCAGGCAGCCCAGGGCCACGCCGCGGCTCCTA CG160093-02 DNA Sequence TCTGCAGCTGCAGGGAGAGAGAGGAGGAACCCCGTGCGATTCTAGAGACGATTTCACAACAAGG AGAAATCAGCTTTGTGCTTACATGCCGAGCAGCCACCACGGTTCTTCTTTGCCTGTCCTCGGGG GAAATCAGGGCTCTGAGAGTGGAGATCGAGATGGGCTAGTGGGTGGCGGATGCGACGCTGCACG GCCAGACCCTGGACTGTGTTTTCACC ATGGAGCAGCTGAGCTCAGCAAACACCCGCTTCGCCTT GGACCTGTTCCTGGCGTTGAGTGAGAACAATCCGGCTGGAAACATCTTCATCTCTCCCTTCAGC ATTTCATCTGCTATGGCCATGGTTTTTCTGGGGACCAGAGGTAACACGGCAGCACAGCTGTCCA AGACTTTCCATTTCAACACGGTTGAAGAGGTTCATTCAAGATTCCAGAGTCTGAATGCTGATAT CAACAAACGTGGAGCGTCTTATATTCTGAAACTTGCTAATAGATTATATGGAGAGAAAACTTAC AATTTCCTTCCTGAGTTCTTGGTTTCGACTCAGAAAACATATGGTGCTGACCTGGCCAGTGTGG ATTTTCAGCATGCCTCTGAAGATGCAAGGAAGACCATAAACCAGTGGGTCAAAGGACAGACAGA AGGAAAAATTCCGGAACTGTTGGCTTCGCGCATGGTTGATAACATGACCAAACTTGTGCTAGTA AATGCCATCTATTTCAAGGGAAACTGGAAGGATAAATTCATGAAACAAGCCACGACGAATGCAC CATTCAGATTGAATAAGAAAGACAGAAAAACTGTGAAAATGATGTATCAGAAGAAAAAATTTGC ATATCGCTACATCGAGGACCTTAAGTGCCGTGTGCTGGAACTGCCTTACCAAGGCGACGAGCTC AGCATGGTCATCCTGCTGCCGGATGACATTGAGGACGAGTCCACGGGCCTGAAGAAGATTGAGG AACAGTTGACTTTGGAAAAGTTGCATGAGTGGACTAAACCTGAGAATCTCGATTTCATTGAAGT TAATGTCAGCTTGCCCAGGTTCAAACTGGAAGAGAGTTACACTCTCAACTCCGACCTCGCCCGC CTAGGTGTGCAGGATCTCTTTAACAGTAGCAAGGCTGATCTGTCTGGCATGTCAGGAGCCAGAG ATATTTTTATATCAAAAATTGTCCACAAGTCATTTGTGGAAGTGAATGAAGAGGGAACAGAGGC GGCAGCTGCCACAGCAGGCATCGCAACTTTCTGCATGTTGATGCCCGAAGAAAATTTCACTGCC GACCATCCATTCCTTTTCTTTATTCGGCATAATTCCTCACGTAGCATCCTATTCTTGGGGAGAT TTTCTTCCCCTTAG AAGAAAGAGACTGTAGCAATACAAAAATCAAGCTTAGTGCTTTATTACCT GAGTTTTTAATAGAGCCAATATGTCTTATATCTTTACCAATAAAACCACTGTCCAGAAACAAAA AAAAAAAAAAAAAA ORF Start: ATG at 283                      ORF Stop: TAG at 1420 SEQ ID NO: 30               379 aa         MW at 42741.3 kD NOV7b, MEQLSSANTRFALDLFLALSENNPAGNIFISPFSISSAMANVPLGTRGNTAAQLSKTFHFNTVE CG160093-02 Protein Sequence EVHSRFQSLNADINKRGASYILKLANRLYGEKTYNFLPEFLVSTQKTYGADLASVDFQHASEDA RKTINQWVKGQTEGKIPELLASGMVDNNTKLVLVNAIYFKGNWKDKFMKEATTNAPFRLNKKDR EWTKPENLDFIEVNVSLPRFKLEESYTLNSDLARLGVQDLFNSSKADLSGMSGARDIFISKIVH KTVKMNYQKKKFAYGYIEDLKCRVLELPYQGEELSMVILLPDDIEDESTGLKKIEEQLTLEKLH KSFVEVNEEGTEAAAATAGIATFCMLMPEENFTADHPFLFFIRHNSSGSILFLGRFSSP

[0382] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B. TABLE 7B Comparison of NOV7a against NOV7b. Identities/ NOV7a Residues/ Similarities for the Protein Sequence Match Residues Matched Region NOV7b 1 . . . 362 362/379 (95%) 1 . . . 379 362/379 (95%)

[0383] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C. TABLE 7C Protein Sequence Properties NOV7a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 10; pos. chg 1; neg. chg 1 H-region: length 3; peak value 5.12 PSG score: 0.72 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −4.07 possible cleavage site: between 48 and 49 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = −2.97 Transmembrane 28-44 PERIPHERAL Likelihood =  2.49 (at 314) ALOM score: −2.97 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 35 Charge difference: 3.5 C(2.5)-N(−1.0) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 1b (cytoplasmic tail 28 to 362 MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 7.63 Hyd Moment(95): 4.21 G content: 0 D/E content: 2 S/T content: 3 Score: −5.24 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: KKDRKTVKMMYQKKKFA at 172 content of basic residues: 11.3% NLS Score: 0.02 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: too long tail Dileucine motif in the tail: found LL at 214 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 89 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 34.8% nuclear 21.7% mitochondrial 21.7% cytoplasmic  8.7% vesicles of secretory system  4.3% vacuolar  4.3% peroxisomal  4.3% endoplasmic reticulum >> indication for CG160093-01 is nuc (k = 23)

[0384] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7D. TABLE 7D Geneseq Results for NOV7a NOV7a Identities/ Residues/ Similarities for Geneseq Protein/Organism/Length [Patent #, Match the Matched Expect Identifier Date] Residues Region Value AAB43755 Human cancer associated protein 1 . . . 362 362/379 (95%) 0.0 sequence SEQ ID NO: 1200 - Homo 59 . . . 437  362/379 (95%) sapiens, 437 aa. [WO200055350-A1, 21 SEP. 2000] AAR94367 Human elastase inhibitor - Homo 1 . . . 362 362/379 (95%) 0.0 sapiens, 379 aa. [WO9610418-A1, 1 . . . 379 362/379 (95%) 11 APR. 1996] AAR64159 Human elastase inhibitor - Homo 1 . . . 362 362/379 (95%) 0.0 sapiens, 379 aa. [US5370991-A, 1 . . . 379 362/379 (95%) 06 DEC. 1994] AAY55841 Human cytoplasmic antiproteinase-3 1 . . . 362 186/380 (48%) 5e−98 protein (CAP-3) - Homo sapiens, 376 1 . . . 376 250/380 (64%) aa. [WO9957273-A2, 11 NOV. 1999] AAR99254 Cytoplasmic antiproteinase-3 protein - 1 . . . 362 186/380 (48%) 5e−98 Homo sapiens, 376 aa. 1 . . . 376 250/380 (64%) [WO9624650-A2, 15 AUG. 1996]

[0385] In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7E. TABLE 7E Public BLASTP Results for NOV7a NOV7a Identities/ Protein Residues/ Similarities for Accession Match the Matched Expect Number Protein/Organism/Length Residues Portion Value P30740 Leukocyte elastase inhibitor (LEI) 1 . . . 362 362/379 (95%) 0.0 (Monocyte/neutrophil elastase 1 . . . 379 362/379 (95%) inhibitor) (M/NEI) (EI) - Homo sapiens (Human), 379 aa. P05619 Leukocyte elastase inhibitor (LEI) - 1 . . . 362 297/379 (78%) e−169 Equus caballus (Horse), 379 aa. 1 . . . 379 326/379 (85%) Q9D154 1190005M04Rik protein (RIKEN 1 . . . 362 291/379 (76%) e−167 cDNA 1190005M04 gene) (Serine 1 . . . 379 330/379 (86%) protease inhibitor EIA) - Mus musculus (Mouse), 379 aa. P80229 Leukocyte elastase inhibitor (LEI) 1 . . . 362 291/379 (76%) e−166 (Leucocyte neutral proteinase inhibitor) 1 . . . 378 332/379 (86%) (LNPI) - Sus scrofa (Pig), 378 aa. S38962 serpin - pig, 378 aa. 1 . . . 362 291/379 (76%) e−165 1 . . . 378 330/379 (86%)

[0386] PFam analysis indicates that the NOV7a protein contains the domains shown in the Table 7F. TABLE 7F Domain Analysis of NOV7a Identities/ NOV7a Similarities Pfam Match for the Expect Domain Region Matched Region Value serpin 1 . . . 136  58/142 (41%) 1.3e−54 120/142 (85%) serpin 137 . . . 362  117/233 (50%)  5.2e−115 208/233 (89%)

Example 8

[0387] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A. TABLE 8A NOV8 Sequence Analysis SEQ ID NO: 31              1697 bp NOV8a, CAGTGTGCTCGAATTCGCCCTTAACCGGCAGG ATGTCGGACGTGCGGCTGCCACCGCTACGCGC CG163133-02 DNA Sequence CCTGGACGACTTTGTTCTGGGGTCGGCGCGTCTCGCGGCTCCGGATCCATGCGACCCGCAGCGA TGGTGCCACCGCGTCATCAACAACCTCCTCTACTACCAAACCAACTACCTTCTCTGCTTCGGCA TCGGCCTCGCTCTCGCCGGGTACGTGCGGCCACTTCAThCGCTCCTGAGCGCGCTGGTAGTGGC GGTGGCCCTCGGCGTGCTGGTGTGGGCAGCTGAGACCCGCGCAGCTGTGCGCCGCTGCCGCCGC AGCCACCCTGCAGCCTGCCTGGCCGCAGTGCTTGCCGTCGGCCTCCTGGTGCTCTGGGTCGCGG GCGGCGCTTGCACCTTCCTGTTCAGCATCGCCGGGCCGGTGCTTCTGATCCTGGTGCACGCCTC GTTGCGCCTGCGCAACCTTAAGAACAAGATTGAGAACAAGATCGAGAGCATTGGTCTCAAGCGG ACGCCAATGGGCCTGCTACTAGAGGCACTGGGACAAGAGCAGGAGGCTGGATCCTAG GCCCCTG GGATCTGTACCCAGGACCTGGAGAATACCACCCCACCCCCAGCCCATAATTGGGACCCAGAGCC CTTTCCCAGCACTTAAACACGAGCCTAGAGCCGCCTGCCCAAACAAAAAAGGGCGA ORF Start: ATG at 33                       ORF Stop: TAG at 567 SEQ ID NO: 32               178 aa         MW at 19257.6 kD NOV8a, MSEVRLPPLRALDDFVLGSARLAAPDPCDPQRWCHRVINNLLYYQTNYLLCFGIGLALAGYVRP CG163133-02 Protein Sequence LHTLLSALVVAVALGVLVWAAETRAAVRRCRRSHPAACLAAVLAVGLLVLWVAGGACTFLFSIA GPVLLILVHASLRLRNLKNKIENKIESIGLKRTPNIGLLLEALCQEQEAGS SEQ ID NO: 33               581 bp NOV8b, GCAGTGTGTGGAATCGCCCTTAACCGGCAGG ATGTCGGACGTGCCGCTGCCACCGCTACGCGCC CG163133-01 DNA Sequence CTGGACGACTTTGTTCTGGGGTCGGCGCGTCTGGCGGCTCCGGATCCATGCGACCCGCAGCGAT GGTGCCACCGCGTCATCAACAACCTCCTCTACTACCAAACCAACTACCTTCTCTGCTTCGGCAT CCGCCTCGCTCTCGCCGGGCACGTGCCGCCACTTCATACGCTCCTAAGCGCCCTGGTAGTGGCG GTGGCCCTCCGCGTGCTGGTGTGGGCAGCTGAGACCCGCGCAGCTGTGCGCCGCTGCCGCCGCA GCCACCCTGCAGCCTGCCTGGCCGCAGTGCTTGCCGTCGGCCTCCTGGTGCACGCCTCGTTGCG CCTGCGCAACCTTAAGAACAAGATTGAGAACAAGATCGAGAGCATTGGTCTCAAGCGGACGCCA ATGGGCCTGCTACTAGAGGCACTGGGACAAGAGCAGGAGGCTGGATCCTAG GCCCCTGGGATCT GTACCCAGGACCTGGAGAATACCACCCCACCCCCAGCCCATAATTGGGACCCAGAGCCCTTTCC CAGCA ORF Start: ATG at 32                       ORF Stop: TAG at 497 SEQ ID NO: 34               155 aa         MW at 16888.7 kD NOV8b, MSEVRLPPLRALDDFVLGSARLAAPDPCDPQRWCHRVINNLLYYQTNYLLCFGIGLALAGHVRP CG163133-01 Protein Sequence LHTLLSALVVAVALGVLVWAAETRAAVRRCRRSHPAACLAAVLAVGLLVHASLRLRNLKNKIEN KIESIGLKRTPMGLLLEALGQEQEAGS

[0388] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 8B. TABLE 8B Comparison of NOV8a against NOV8b. Identities/ Similarities NOV8a Residues/ for the Protein Sequence Match Residues Matched Region NOV8b 1 . . . 178 154/178 (86%) 1 . . . 155 155/178 (86%)

[0389] Further analysis of the NOV8a protein yielded the following properties shown in Table 8C. TABLE 8C Protein Sequence Properties NOV8a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 10; pos. chg 2; neg. chg 1 H-region: length 2; peak value −2.04 PSG score: −6.44 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −3.41 possible cleavage site: between 59 and 60 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 4 INTEGRAL Likelihood =  −0.59 Transmembrane  49-65 INTEGRAL Likelihood =  −9.66 Transmembrane  68-84 INTEGRAL Likelihood = −10.14 Transmembrane 100-116 INTEGRAL Likelihood =  −7.38 Transmembrane 120-136 PERIPHERAL Likelihood =  8.43 (at 155) ALOM score: −10.14 (number of TMSs: 4) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 56 Charge difference: 1.0 C(1.5)-N(0.5) C > N: C-terminal side will be inside >>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 4.19 Hyd Moment(95): 1.05 G content: 0 D/E content: 2 S/T content: 1 Score: −5.78 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.1% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: SEVR none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 55.6%: endoplasmic reticulum 11.1%: mitochondrial 11.1%: Golgi 11.1%: vacuolar 11.1%: cytoplasmic >> indication for CG163133-02 is end (k = 9)

[0390] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8D. TABLE 8D Geneseq Results for NOV8a NOV8a Identities/ Residues/ Similarities for Geneseq Protein/Organism/Length [Patent #, Match the Matched Expect Identifier Date] Residues Region Value AAE14754 Human CCR5 chemokine 1 . . . 178  178/178 (100%) 2e−98 receptor-interacting protein P2 - Homo 1 . . . 178  178/178 (100%) sapiens, 178 aa. [EP1207202-A1, 22 MAY 2002] ABB97608 - Homo sapiens, 178 aa. 1 . . . 178  178/178 (100%) 2e−98 [WO200222660-A2, 21 MAR. 2002] AAB94612 Human protein sequence SEQ ID 1 . . . 178 177/178 (99%) 4e−98 NO: 15456 - Homo sapiens, 178 aa. 1 . . . 178 178/178 (99%) [EP1074617-A2, 07 FEB. 2001] AAE14761 Human CCR5 chemokine 1 . . . 178 177/178 (99%) 1e−97 receptor-interacting protein P2 mutant 1 . . . 178 177/178 (99%) (G53A) - Homo sapiens, 178 aa. [EP1207202-A1, 22 MAY 2002] AAE14760 Human CCR5 chemokine 1 . . . 178 177/178 (99%) 2e−97 receptor-interacting protein P2 mutant 1 . . . 178 177/178 (99%) (G157R) - Homo sapiens, 178 aa. [EP1207202-A1, 22 MAY 2002]

[0391] In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8E. TABLE 8E Public BLASTP Results for NOV8a NOV8a Identities/ Protein Residues/ Similarities Accession Match for the Expect Number Protein/Organism/Length Residues Matched Portion Value O60831 JM4 protein - Homo sapiens (Human), 1 . . . 178  178/178 (100%) 5e−98 178 aa. 1 . . . 178  178/178 (100%) Q9JIG8 DXImx39e protein (DNA segment, 1 . . . 178 162/178 (91%) 6e−89 Chr X, Immunex 39, expressed) - Mus 1 . . . 178 166/178 (93%) musculus (Mouse), 178 aa. Q9ES40 Glutamate transporter EAAC1 3 . . . 176  78/174 (44%) 4e−41 interacting protein - Rattus norvegicus 2 . . . 175 119/174 (67%) (Rat), 188 aa. O75915 JWA protein (HSPC127) (Vitamin A 3 . . . 175  79/173 (45%) 4e−41 responsive, cytoskeleton related) - 2 . . . 174 117/173 (66%) Homo sapiens (Human), 188 aa. Q9DB37 5930404D22Rik protein (RIKEN 3 . . . 175  78/173 (45%) 1e−40 cDNA 5930404D22 gene) (JWA 2 . . . 174 118/173 (68%) protein) - Mus musculus (Mouse), 188 aa.

Example 9

[0392] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A. TABLE 9A NOV9 Sequence Analysis SEQ ID NO: 35              6240 bp NOV9a, CTTTCTGTCTCTCGGGACCCTTATTTCTTCGTCACGGTGTCCAGGACCATTTTGACCCTGTCGG CG165528-01 DNA Sequence CCCCGGCACCCCCCCGCCGCACCCCAGCCCCGAGC ATGGGACGGCGCTGCTCCAGCGCGGGGGG CTGTTTTCTTCTGTGCCTCTCGCTGCTGCTCCTCGGCTGCTGGGCGGAGCTGGGCACCGGGCTG GAGTTTCCGGGCGCCGAGGGCCAATGGACGCGCTTCCCCAACTGGAACGCCTGCTGCGAGAGCG AGATGAGCTTCCAGCTCAAGACTCGCAGCGCCCGCGGCCTCGTACTCTACTTCGACGACGAGCG CTTCTGCGACTTCCTGGAGCTGATTCTGACGCGCGGCGGCCGCCTGCACCTCAGCTTCTCCATC TTCTGCGCTGAGCCTGCGACGCTCCTGGCCGACACGCCGGTTAACGACGGCGCCTGGCACAGCG TGCGCATCCGCCGCCAGTTCCGCAACACCACGCTCTTCATCGACCAGGTGGAGGCCAAGTCGGT GGAGGTCAAGTCCAAGCGCAGGGACATGACGGTGTTCAGCGGCCTTTTCGTCCGGGGGCTGCCC CCGGAACTGCGCGCCGCGGCGCTCAAGCTCACCCTGGCCTCGGTGAGGGAGCCGGAGCCCTTCA AGGGGTCGATTCGTGACGTGAGGGTCAACTCCTCGCAGGTCCTGCCCGTCGACAGCGGCGAGGT GAAGCTGGACGATGAGCCGCCCAACAGCGGCGGGGGAAGCCCGTGCGAGGCGGGCGAGGAGGGC GAGGGCGGGGTGTGCCTCAACGGAGGTGTGTGCTCCGTGGTGGACGACCAGGCCGTGTGCGACT GCTCGCGAACCGGCTTCCGCCGCAAGGACTGCAGCCAAGAAGACAACAATGTCGAAGGTCTGGC GCACCTGATGATGGGCGACCAAGGTAAAAGTAAAGGAAAAGAAGAATATATTGCCACGTTCAAA CGATCTGAATACTTCTGCTACGACTTGTCTCAAAACCCCATTCAAAGCAGCAGTGATGAAATAA CTCTGTCATTTAAAACCCTTCAGAGGAATGGACTGATGCTTCACACTCGGAAATCGGCTGATTA TGTCAATCTTGCCCTGAAAAATGGAGCTGTCTCTCTGGTCATTAATTTGGGATCAGGGGCCTTT GAAGCACTAGTGGAGCCTGTGAATGGAAAGTTTAATGATAATGCCTGGCATGATGTGAAAGTCA CCAGGAATCTGCGTCAGCACTCAGGCATTGGACACGCTATGGTAAACAAACTACATTGTTCGGT GACAATATCAGTGGATGGGATTCTTACCACAACGGGCTACACGCAAGAAGATTATACCATGCTG GGGTCTGATGACTTTTTCTATGTTGGAGGCAGTCCCAGCACAGCCGACCTTCCAGGGTCACCAG TCAGTAACAACTTTATGGGCTGTCTCAAAGAGGTTGTATATAAAAATAATGATGTGAGGCTGGA ATTATCTCGACTTGCCAAGCAAGGAGATCCTAAGATGAAGATCCATCGAGTGGTCGCATTTAAA TGTGAGAATGTTGCAACTTTAGACCCAATCACCTTTGAAACCCCAGAGTCTTTCATCTCTTTGC CTAAATGGAATGCAAAGAAAACTGGCTCCATATCATTTGATTTCCGTACAACAGAGCCAAATGG CCTCATCTTATTTAGCCATGGCAAGCCAAGACATCAGAAAGATGCCAAGCACCCACAGATGATA AAGGTGGACTTCTTTGCTATTGAGATGCTAGATCGCCACCTCTACCTCCTCCTGGACATGCGGT CAGGTACTATAAAAATAAAAGCCCTGTTGAAGAAAGTGAATGATGGAGAATGGTATCATGTGGA CTTCCAGAGAGACGGACGGTCACGTACCATTTCTGTCAACACGTTGCGTACTCCCTACACTGCT CCTGGTGAGAGTGAGATTCTCGACCTGGATGATGAGTTGTACCTGGGGGGGCTGCCAGAAAATA AAGCTGGCCTTGTCTTCCCCACCGAGGTGTCGACTGCTCTGCTCAACTATGGCTACGTGGGCTG CATCAGGGATTTGTTCATCGATGGCCAAAGCAAAGATATCCGGCAAATGGCTGAAGTTCAAAGT ACTGCTGGAGTGAAGCCTTCCTGCTCAAAGGAAACAGCAAAACCGTGCCTTAGCAACCCTTGCA AAAACAATGGCATGTGCAGGGATGGGTGGAACAGATATGTCTGTGATTGTTCCGCAACAGGCTA TCTTGGCAGGTCCTGTGAGAGAGAGGCAACGGTTTTGAGCTATGATGGGAGCATGTTTATGAAA ATTCAGCTCCCCGTAGTCATGCATACCGAGGCTGAGGATGTTTCCTTACGGTTCCGATCCCAGC GTGCATATGGCATTCTGATGGCAACCACTTCTAGAGACGCTGCTGACACCCTCCGCCTCGAGCT AGACGCAGGACGTGTGAAACTGACGGTCAATCTAGATTGTATCACGATTAACTGTAATTCCAGC AAAGGTCCCGAGACTCTTTTTGCTGGCTTTAACCTCAATGATAACGACTGGCACACAGTGCGTG TAGTTCCGCGTGGAAAAAGTTTAAAGTTAACAGTCGATGACCAACAGGCCATGACAGGTCAAAT GGCAGGTGATCATACTACGCTGGAGTTCCATAACATAGAGACTGGCATCATCACAGAACGACGG TATCTTTCTTCTGTCCCCTCCAACTTCATTGGACACCTGCAGAGCTTGACATTTAATGGAATGG CATACATTGACCTGTGTAAAAATGGCGACATAGATTACTGTGAGCTTAATGCCAGATTTGGCTT CAGGAACATCATAGCAGATCCTGTCACCTTCAAGACCAAATCGAGCTATGTTGCCTTAGCTACC TTGCAAGCCTACACTTCTATGCATCTTTTTTTCCAGTTCAAGACAACATCCCTAGATGGATTAA TTCTATATAACAGTGGGGATGGAAATGACTTTATTGTGGTTGAATTAGTTAAAGGGTACTTACA TTACGTGTTTGATTTCGGAAATGGTGCTAACCTCATCAAAGGAAGCTCAAATAAACCTCTCAAT GACAATCAGTGGCACAACGTGATGATATCAAGGGACACCAGCAACCTCCACACTGTAAAGATTG ACACAAAAATCACAACGCAAATCACCGCCGGAGCCACGAACTTAGACCTCAAGAGTGACTTATA TATAGGAGGAGTAGCTAAAGAAACATACAAATCCTTACCAAAACTTGTACATGCCAAAGAAGGC TTTCAAGGCTGCCTGGCATCAGTTGATTTAAATGGACGGCTTCCGGACCTCATCTCCGATGCTC TTTTCTGCAACGGACAGATCGAGAGAGGATGTGAAGGGCCCAGCACAACCTGCCAAGACGACTC ATGTTCCAATCAAGGTGTGTGCTTGCAACAATGGGATGGCTTCAGCTGTGACTGTAGTATGACT TCCTTCAGTCGACCACTCTGCAATGACCCTGGGACGACATATATCTTTAGCAAAGGTGGTGGAC AAATCACGTATAAGTGGCCTCCTAATGACCGACCCAGTACACGAGCAGACAGACTGGCCATAGG TTTTAGCACTGTTCAGAAAGAAGCCGTATTGGTGCGAGTGGACAGTTCTTCACGCTTGGGTGAC TACCTAGAACTGCATATACACCACGGAAAAATTGGAGTTAAGTTTAATGTTGGGACAGATGACA TCGCCATTGAAGAATCCAATGCAATCATTAATGATGCGAAATACCATGTAGTTCGTTTCACGAG GAGTGGTGGCAATGCCACCTTGCAGGTGGACAGCTGGCCAGTGATCGAGCGCTACCCTGCAGGA AACAATGATAACGAGCGCCTGGCGATTGCTAGACAGCGAATTCCATATCGACTTCGTCGAGTAG TTGATGAATGGCTACTCGACAAAGGGCGTCAGCTCACAATCTTCAATAGCCAAGCAACCATAAT AATTGGCGGGAAAGAGCAGGGCCAGCCCTTCCAGGGCCAGCTCTCTGGGCTGTACTACAATGGC TTGAAAGTTCTGAATATGGCAGCCGAAAACGATGCCAACATCGCCATAGTGGGAAATGTGAGAC TGGTTGGTGAAGTGCCTTCCTCTATGACAACTGAGTCAACAGCCACTGCCATGCAATCAGAGAT GTCCACATCAATTATGGAGACTACCACGACCCTGGCTACTAGCACAGCCAGAAGAGGAAAGCCC CCGACAAAAGAACCCATTAGCCAGACCACAGATGACATCCTTGTGGCCTCAGCAGAGTGTCCCA GCGATGATGAGGACATTGACCCCTGTGAGCCGAGCTCAGGTGGGTTAGCCAACCCAACCCGAGC AGGCGGCAGAGAGCCGTATCCAGGCTCAGCAGAAGTGATCCGGGAGTCCAGCAGCACCACGGGT ATGGTCGTTGGGATAGTAGCCGCTGCCGCCCTGTGCATCCTTATCCTCCTCTATGCCATGTACA AGTACAGAAACCGGGATGAAGGCTCATACCATGTGGACGAGAGTCGAAACTACATCAGTAACTC AGCACAGTCCAATGGGGCTGTTGTAAAGGAGAAACAACCCAGCAGTGCGAAAAGCTCCAACAAA AATAAGAAAAACAAGGATAAAGAGTATTATGTCTGA TCCCAAGATCTTAAATGGACACTTGTAT AGAAATAGTCTTCATTTTATCTGAGACATAATATAAACTTATTTACTTTCCTTTTTATGAAGCA CATACAAAAGAAGACAGAGAATGCAATCAGGAAGGAAAGACTTTTTAAAAAATAAAAACAAGTA TCTCATGCTCTTGTTTCTCAAAAAAGAAAAACAAAAAACAAAAAACAGGGGCCAATAAATTCCC TAACATCCACAGTGTTTTCATTTACTCTGCTTGTCTTTATGTTGCTGGAACATTTCTAAAAGAC AGTGATGACCGCACGCATTCATAAAGCAAAGGAGTACTACAGCATCAAGGCACAACACAAAAAC CAACACAAAACATAACACAAAAAAGAAGCTACCTATGATCCTCGATTTAGCCAAAGTGCTAGCG CTTTCCTGAGAAGTCAGTCCAATTGCCAGAGAAGACTGTCCTTTTGAGTGACTCAACCTGCAAA CCTTTAAGAGTTTGCCGCCTGGTGCAACTGGAGCAGTGGTTGGAACTTGCATTTGAAACAAAGT GCTGGCTTTTTTGAAGACTTGTGTACGAACACATTCAAAAAGCCCCTTTCTGGTTGTGAGAGAG GAAAAAAAAAAAGTATGGAGGCCTTATTTTCAAAAATGTGAAATATAAGGCACGTTTTCACAAA ATTTCAAACAAAAACAAGAGGGCAATAGATGCAATCATTGGGAAATTTTCATGCACGCTTATTA TGTTATTACATATGTTTATATAAAATCCATCTCTGTGTGCTTTCTGGACTGTGATAAGTGACGT TTTATAGCCTGTTGTATAGAAAATGCAAAATATATCTCTGCTCTTCAGCCATTTTTGGTAAATT CAATGTTATAAGTGTTGCTAAGTATAGGGAGTTTTATGACATCAGAGCAACAATTATTTCAGTT GGGTTTTTCTTTTTTTTGCCACCATTATAAATTGCCACAATTACTTACTTTTATTTTTTAAAGA AATTACAGTGTAGTGTTTATTCTAAGGAAGATATGTATGAATGTATATACAAAGACTCAGCTAC TTCTTTTCTTATATGTACAGCCTTCATTCTGTTGCAATTAAGTTTTAGTACTTGTATGAAAGGT CTGAATTAGAAAGTCACATATATACATATGTATCTTATAATCTTTTCTCCCTGAAATACTCACA TTCCCACATACATTCACTATTTTCACACACACACACACACACACACACACACACACACACACAC ACGAATCCACAGCAATCCATCAGATATGCTGGAAGATCCAAACGTGCATACAGTAGCAAATATT TATTGACAAATTGAAAAGCAGGAAGGAAGAGGGTTGTGCCAAGGTATTGATGACAAATGGGGTG ATTTGCTTCATTGAGATCTTGCTCCCAGGTAACCTTAAGAAGATTTTAGTCCCTAAAGAAATGA ACCTTTCCTTATCAAATAGAATATCACTGATATACTGCTGCATGAATAAGAACCATTATGTGGG CAGGTTATGGAAGCAAAATTGGTTAATCTACACCTTAACTCTGGCTGCTGCAATTGAAAACTTT CTTTCTAATAAAATAATATATATATCTCTGAA ORF Start: ATG at 100                      ORF Stop: TGA at 4642 SEQ ID NO: 36              1514 aa         MW at 166226.0 kD NOV9a, MGTALLQRGGCFLLCLSLLLLGCWAELGSGLEFPGAEGQWTRFPKWNACCESEMSFQLKTRSAR CG165528-01 Protein Sequence GLVLYFDDEGFCDFLELILTRGGRLQLSFSIFCAEPATLLADTPVNDGAWHSVRIRRQFRNTTL FIDQVEAKWVEVKSKRRDMTVFSGLFVGGLPPELRAAALKLTLASVREREPFKGWIRDVRVNSS QVLPVDSGEVKLDDEPPNSGGGSPCEAGEEGEGGVCLNGGVCSVVDDQAVCDCSRTGFRGKDCS QEDNNVEGLAHLMMGDQGKSKGKEEYIATFKGSEYFCYDLSQNPIQSSSDEITLSFKTLQRNGL MLHTGKSADYVNLALKNGAVSLVINLGSGAFEALVEPVNGKFNDNAWHDVKVTRNLRQHSGIGH AMVNKLHCSVTISVDGILTTTGYTQEDYTMLGSDDFFYVGGSPSTADLPGSPVSNNFMGCLKEV VYKNNDVRLELSRLAKQGDPKMKIHGVVAFKCENVATLDPITFETPESFISLPKWNAKKTGSIS FDFRTTEPNGLILFSHGKPRHQKDAKHPQMIKVDFFAIEMLDGHLYLLLDMGSGTIKIKALLKK VNDGEWYHVDFQRDGRSGTISVNTLRTPYTAPGESEILDLDDELYLGGLPENKAGLVFPTEVWT ALLNYGYVGCIRDLFIDGQSKIRQMAEVAQSTAGVKPSCSKETAKPCLSNPCKNNGMCRDGWNR YVCDCSGTGYLGRSCEREATVLSYDGSMFMKIQLPVVMHTEAEDVSLRFRSQRAYGILMATTSR DSADTLRLELDAGRVKLTVNLDCIRINCNSSKGPETLFAGYNLNDNEWHTVRVVRRGKSLKLTV DDQQAMTGDMAGDHTRLEFHNIETGIITERRYLSSVPSNFIGHLQSLTFNGMAYIDLCKNGDID YCELNARFGFRNIIADPVTFKTKSSYVALATLQAYTSMHLPFQFKTTSLDGLILYNSGDGNDFI VVELVKGYLHYVFDLCNGANLIKGSSNKPLNDNQWHNVMISRDTSNLHTVKIDTKITTQITAGA RNLDLKSDLYICGVAKETYKSLPKLVHAKEGFQGCLASVDLNGRLPDLISDALFCNGQIERGCE GPSTTCQEDSCSNQGVCLQQWDGFSCDCSMTSFSGPLCNDPGTTYIFSKGGGQITYKWPPNDRP STRADRLAIGFSTVQKEAVLVRVDSSSGLGDYLELHIHQGKIGVKFNVGTDDIAIEESNAIIND GKYHVVRFTRSGGNATLQVDSWPVIERYPACNNDNERLAIARQRIPYRLGRVVDEWLLDKGRQL TIPNSQATIIIGGKEQGQPFQGQLSGLYYNGLKVLNMAAENDANIAIVGNVRLVGEVPSSMTTE STATANQSEMSTSIMETTTTLATSTARRGKPPTKEPISQTTDDILVASAECPSDDEDIDPCEPS SGGLANPTRAGGREPYPGSAEVIRESSSTTGMVVGIVAAAALCILILLYAMYKYRNRDEGSYHV DESRYISNSAQSNGAVVKEKQPSSAKSSNKNKKNKDKEYYV SEQ ID NO: 37              1611 bp NOV9b, AAACTTTGCCTCCCGCGGCGGCTGCCCCTCCGCCGGCGCCCCGCC ATGTACCAGAGGATGCTCC CG165528-02 DNA Sequence GGTGCGGCGCCGAGCTGGGCTCGCCCGGGGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGCAGG GGGGCGCCTGGCCCTGCTTTGGATAGTCCCGCTCACCCTCAGCGGCCTCCTAGGAGTGGCGTGG GGGGCATCCAGTTTGGGAGCGCACCACATCCACCATTTCCATGGCAGCAGCAAGCATCATTCAG TGCCTATTGCAATCTACAGGTCACCGGCATCCTTGCGAGGCGGACACGCTGGGACGACATATAT CTTTAGAAAGGTGGTAGGACAAATCACGTATAAGTGGCCTCCTAATGACCGACCCAGTACACGA GCAGACAGACTGGCCATAGGTTTTAGCACTGTTCAGAAAGAAGCCGTATTGGTGCGAGTGGACA GTTCTTCAGGCTTGGGTGACTACCTAGAACTGCATATACACCAGGGAAAAATTGGAGTTAAGTT TAATGTTGGGACAGATGACATCGCCATTGAAGAATCCAATGCAATCATTAATGATGGGAAATAC CATGTAGTTCGTTTCACGAGGAGTGGTGGCAATGCCACGTTGCAGGTGGACAGCTGGCCAGTGA TCGAGCGCTACCCTGCAGGAAACAATGATAACGAGCGCCTGGCGATTGCTAGACAGCGAATTCC ATATCGACTTGGTCGAGTAGTTGATGAATGGCTACTCGACAAAGGGCGTCAGCTCACAATCTTC AATAGCCAAGCAACCATAATAATTGGCGGGAAAGAGCAGGGCCAGCCCTTCCAGGGCCAGCTCT CTGGGCTGTACTACAATGGCTTGAAAGTTCTGAATATGGCAGCCGAAAACGATGCCAACATCGC CATAGTGGGAAATGTGAGACTGGTTGGTGAAGTGCCTTCCTCTATGACAACTGAGTCAACAGCC ACTGCCATGCAATCAGAGATGTCCACATCAATTATGGAGACTACCACGACCCTGGCTACTAGCA CAGCCAGAAGAGGAAAGCCCCCGACAAAAGAACCCATTAGCCAGACCACAGATGACATCCTTGT ACTGCCATGCAATCAGAGATGTCCACATCAATTATGGAGACTACCACGACCCTGGCTACTAGCA CAGCCAGAAGAGGAAAGCCCCCGACAAAAGAACCCATTAGCCAGACCACAGATGACATCCTTGT GGCCTCAGCAGAGTGTCCCAGCGATGATGAGGACATTGACCCCTGTGAGCCGAGCTCAGGTGGG TTAGCCAACCCAACCCGAGCAGGCGGCAGAGAGCCGTATCCAGGCTCAGCAGAAGTGATCCGGG AGTCCAGCAGCACCACGGGTATGGTCGTTGGGATAGTAGCCGCTGCCGCCCTGTGCATCCTTAT GTGCGAAAAGCTCCAACAAAAATAAGAAAAACAAGGATAAAGAGTATTATGTCTGA TCCCAGCA TCTTAAATGGACACTTGTATAGAAATAGTCTTCATTTTATCTGAGACATAATATAAACTTATTT ACTTTCCTTTTTATGAAGCACATACAAAAGAAGACAGGGAATGCAATCAGGAAGGAAAGACTTT TTAAAAAATAA ORF Start: ATG at 46                       ORF Stop: TGA at 1462 SEQ ID NO: 38               472 aa         MW at 50423.1 kD NOV9b, MYQRMLRCGAELGSPGGGGGGGGGGGAGGRLALLWIVPLTLSGLLGVAWGASSLGAHHIHHFHG CG165528-02 Protein Sequence SSKHHSVPIAIYRSPASLRGGHAGTTYIFSKGGGQITYKWPPNDRPSTRADRLAIGFSTVQKEA VLVRVDSSSGLGDYLELHIHQGKIGVKFNVGTDDIAIEESNAIINDGKYHVVRFTRSGGNATLQ VDSWPVIERYPAGNNDNERLAIARQRIPYRLGRVVDEWLLDKGRQLTIFNSQATIIIGGKEQGQ PEQCQLSGLYYNGLKVLNMAAENDANIAIVGNVRLVGEVPSSMTTESTATAMQSEMSTSIMETT TTLATSTARRGKPPTKEPISQTTDDILVASAECPSDDEDIDPCEPSSGGLANPTRAGGREPYPG SAEVIRESSSTTGMVVGIVAAAALCILILLYAMYKYRNRDEGSYHVDESRNYISNSAQSNGAVV KEKQPSSAKSSNKNKKNKDKEYYV

[0393] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B. TABLE 9B Comparison of NOV9a against NOV9b. Identities/ Similarities NOV9a Residues/ for the Protein Sequence Match Residues Matched Region NOV9b 1130 . . . 1514 385/385 (100%)  88 . . . 472 385/385 (100%)

[0394] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C. TABLE 9 C Protein Sequence Properties NOV9a SignalP Cleavage site between residues 26 and 27 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 8; pos. chg 1; neg. chg 0 H-region: length 17; peak value 10.61 PSG score: 6.21 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 7.83 possible cleavage site: between 25 and 26 >>> Seems to have a cleavable signal peptide (1 to 25) ALOM: Klein et al's method for TM region allocation Init position for calculation: 26 Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = −13.59 Transmembrane 1440-1456 PERIPHERAL Likelihood =   2.44 (at 89) ALOM score: −13.59 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 12 Charge difference: −5.0 C(−3.0)-N(2.0) N >= C: N-terminal side will be inside >>> membrane topology: type 1a (cytoplasmic tail 1457 to 1514) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 10.18 Hyd Moment(95): 7.78 G content:  4 D/E content: 1 S/T content:  2 Score: −4.63 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 18 QRG|GC NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.4% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: KKXX-like motif in the C-terminus: KEYY SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: too long tail Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: Leucine zipper pattern (PS00029): *** found *** LQRGGCFLLCLSLLLLGCWAEL at 6 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 70.6 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 44.4%: endoplasmic reticulum 22.2%: Golgi 11.1%: plasma membrane 11.1%: vesicles of secretory system 11.1%: extracellular, including cell wall >> indication for CG165528-01 is end (k = 9)

[0395] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9D. TABLE 9D Geneseq Results for NOV9a NOV9a Identities/ Residues/ Similarities Geneseq Protein/Organism/Length [Patent Match for the Expect Identifier #, Date] Residues Matched Region Value AAM79855 Human protein SEQ ID NO 3501 -  1 . . . 1514 1465/1517 (96%) 0.0 Homo sapiens, 1522 aa. 47 . . . 1522 1466/1517 (96%) [WO200157190-A2, 09 AUG. 2001] AAM78871 Human protein SEQ ID NO 1533 - 147 . . . 1514  1326/1368 (96%) 0.0 Homo sapiens, 1327 aa.  1 . . . 1327 1326/1368 (96%) [WO200157190-A2, 09 AUG. 2001] AAE17600 Human extracellular messenger 19 . . . 1514 1041/1496 (69%) 0.0 (XMES)-2 protein - Homo sapiens, 16 . . . 1438 1210/1496 (80%) 1438 aa. [WO200194587-A2, 13 DEC. 2001] AAU28190 Novel human secretory protein, Seq 16 . . . 1411  975/1426 (68%) 0.0 ID No 359 - Homo sapiens, 1712 aa. 14 . . . 1419 1162/1426 (81%) [WO200166689-A2, 13 SEP. 2001] AAU14241 Human novel protein #112 - Homo 414 . . . 1514   834/1101 (75%) 0.0 sapiens, 1091 aa.  1 . . . 1091  960/1101 (86%) [WO200155437-A2, 02 AUG. 2001]

[0396] In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9E. TABLE 9E Public BLASTP Results for NOV9a NOV9a Protein Residues/ Identities/ Accession Match Similarities for the Expect Number Protein/Organism/Length Residues Matched Portion Value Q63372 Neurexin 1-alpha precursor 1 . . . 1514 1496/1514 (98%) 0.0 (Neurexin I-alpha) - Rattus 1 . . . 1514 1506/1514 (98%) norvegicus (Rat), 1514 aa. Q28146 Neurexin 1-alpha precursor 1 . . . 1514 1503/1530 (98%) 0.0 (Neurexin I-alpha) - Bos taurus 1 . . . 1530 1508/1530 (98%) (Bovine), 1530 aa. A40228 neurexin I-alpha precursor - rat, 1 . . . 1514 1489/1514 (98%) 0.0 1507 aa. 1 . . . 1507 1499/1514 (98%) BAA25504 KIAA0578 protein - Homo sapiens 1 . . . 1514 1496/1514 (98%) 0.0 (Human), 1542 aa (fragment). 47 . . . 1542  1496/1514 (98%) BAC41433 MKIAA0578 protein - Mus 1 . . . 1514 1468/1514 (96%) 0.0 musculus (Mouse), 1525 aa 47 . . . 1525  1473/1514 (96%) (fragment).

[0397] PFam analysis indicates that the NOV9a protein contains the domains shown in the Table 9F. TABLE 9F Domain Analysis of NOV9a Identities/ NOV9a Similarities Pfam Match for the Expect Domain Region Matched Region Value laminin_G  58 . . . 195 46/167 (28%)    4e−12 101/167 (60%)  laminin_G 312 . . . 378 23/81 (28%) 1.4e−08 47/81 (58%) laminin_G 393 . . . 456 17/81 (21%) 0.013 43/81 (53%) laminin_G 515 . . . 662 56/169 (33%)  1.1e−28 114/169 (67%)  EGF 687 . . . 719 13/47 (28%) 0.00049 24/47 (51%) laminin_G 753 . . . 834 26/97 (27%) 0.00016 59/97 (61%) laminin_G  940 . . . 1071 43/163 (26%)  6.4e−16 99/163 (61%)  EGF 1094 . . . 1126 12/47 (26%) 0.00019 26/47 (55%) laminin_G 1163 . . . 1236 22/87 (25%) 3.2e−07 48/87 (55%)

Example 10

[0398] The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A. TABLE 10A NOV10 Sequence Analysis SEQ ID NO: 39              1365 bp NOV10a, ACGCGTGGAGTCCTGCGGGCCGTGGCCACCCAGCAGCGCGGCGCCGTGTTCGTGGACAAGGAGA CG165666-01 DNA Sequence ACCTCACC ATGCCGGGCCTCAGGTTCGACAACATCCAGGGAGATGCAGTTAAAGACTTGATGCT TCGCTTTCTGGGTGAAAAAGCTGCAGCAAAGAGACAAGTCCTAAATGCCGACTCAGTGGAACAA TCTTTTGTTCGATTGAAACAGCTAATCCTCTCGTTTGTCAGGCTGGCACTACTAGTGAAGTTGG GCCTTTTCCAGAATGCTGAGATGGAATTTGAACCCTTCGGAAATCTTGATCAGCCAGATCTTTA TTACGAGTACTACCCGCACGTGTACCCTGGGCGCACGGGCTCCATGGTCCCCTTCTCGATGCGC ATCTTGCACGCGGAGCTTCAGCAGTACCTGGGGAACCCACAGGAGTCGCTGGATAGACTGCACA AGGTGAAGACTGTCTGCAGCAAGATCCTGGCCAATTTGCAGCAACGCTTAGCAGAAGACGGCGG CATGAGCAGCGTGACTCAGGAGGGCAGACAAGCCTCTATCCCGCTGTCGAGGTCACGTCTGGGC CGGGTGATGTACTCCATGGCAAACTGTCTGCTCCTGATGAAGGATTATGTGCTGGCCGTGGACG CGTATCATTCGGTTATCAAGTATTACCCAGAGCAAGAGCCCCAGCTGCTCAGCGGCATCGGCCG GATTTCCCTGCAGATTGGAGACATAAAAACAGCTGAAAAGTATTTTCAAGACGTTGAGAAAGTA ACACAGAAATTAGATGGACTACAGGGTAAAATCATGGTTTTGATGAACAGCGCGTTCCTTCACC TCGGGCAGAATAACTTTGCAGAAGCCCACACGTTCTTCACAGAGATCTTAAGGATGGATCCAAG AAACGCAGTGGCCAACAACAACGCTGCCGTGTGTCTGCTCTACCTGCGCAAGCTCAAGGACTCC CTGCGGCAGCTGGAGGCCATGGTCCAGCAGGACCCCAGGCACTACCTGCACGAGAGCGTGCTCT TCAACCTGACCACCATGTACGAGCTGGAGTCCTCACGGAGCATGCAGAAGAAACAGGCCCTGCT GGAGCCTGTCGCCGGCAAGGAGGGGGACAGCTTCAACACACAGTGCCTCAAGCTGGCCTAG CTG CCTCCAACACACTACGTCAGAACGACCCGGGTCTTTGAAACTGTGTCTTGAAGCTAATGTATTA ATGTGACATGGACGAACTCAATAAAACTCCTGCTTCACTGGTGTCTGCTGCGTGTCTTCTTGGT CCCAAGCCACGGCCCAGCCCAGGACTTCCCCGCAGTTGGTCCGCGTTCAGCCACGCAGTCCCTG CACCTGGGTCACTGTTCATGA ORF Start: ATG at 73                       ORF Stop: TAG at 1147 SEQ ID NO: 40               358 aa         MW at 40766.8 kD NOV1Oa, MPGLRFDNIQGDAVKDLMLRFLGEKAAAKRQVLNADAVEQSFVGLKQLILWFVRLALLVKLGLF CG165666-01 Protein Sequence QNAEMEFEPFGNLDQPDLYYEYYPHVYPGRRGSMVPFSMRILHAELQQYLGNPQESLDRLHKVK TVCSKILANLEQGLAEDGGMSSVTQEGRQASIRLWRSRLGRVMYSMANCLLLMKDYVLAVEAYH SVIKYYPEQEPQLLSGIGRISLQIGDIKTAEKYFQDVEKVTQKLDGLQGKIMVLMNSAFLHLGQ NNFAEAHRFFTEILRMDPRNAVANNNAAVCLLYLGKLKDSLRQLEAMVQQDPRHYLHESVLFNL TTMYELESSRSMQKKQALLEAVAGKEGDSFNTQCLKLA

[0399] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B. TABLE 10B Protein Sequence Properties NOV10a SignalP Cleavage site between residues 65 and 66 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 7; pos. chg 1; neg. chg 1 H-region: length 4; peak value −9.72 PSG score: −14.12 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −6.97 possible cleavage site: between 58 and 59 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = −5.47 Transmembrane 48-64 PERIPHERAL Likelihood =   3.87 (at 174) ALOM score: −5.47 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 55 Charge difference: −4.0 C(−2.0)-N(2.0) N >= C: N-terminal side will be inside >>> membrane topology: type 2 (cytoplasmic tail 1 to 48) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75): 1.36 Hyd Moment (95): 3.47 G content: 2 D/E content: 2 S/T content: 0 Score: −8.05 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 15 LRF|DN NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.5% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: PGLR KKXX-like motif in the C-terminus: CLKL SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: found KLKDSLRQL at 292 VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 89 COIL: Lupas's algorithm to detect coiled-coil regions 218 I 0.66 219 K 0.67 220 T 0.71 221 A 0.71 222 E 0.71 223 K 0.71 224 Y 0.71 225 F 0.71 226 Q 0.71 227 D 0.71 228 V 0.71 229 E 0.71 230 K 0.71 231 V 0.71 232 T 0.71 233 Q 0.71 234 K 0.71 235 L 0.71 236 D 0.71 237 G 0.71 238 L 0.71 239 Q 0.71 240 G 0.71 241 K 0.71 242 I 0.71 243 M 0.71 244 V 0.71 245 L 0.71 246 M 0.71 247 N 0.71 248 S 0.71 249 A 0.71 total: 32 residues Final Results (k = 9/23): 39.1%: mitochondrial 30.4%: cytoplasmic  8.7%: Golgi  8.7%: nuclear  8.7%: endoplasmic reticulum  4.3%: vacuolar >> indication for CG165666-01 is mit (k = 23)

[0400] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10C. TABLE 10C Geneseq Results for NOV10a Identities/ Similarities for Geneseq Protein/Organism/Length NOV10a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value AAB42120 Human ORFX ORF1884 polypeptide 18 . . . 358 341/379 (89%) 0.0 sequence SEQ ID NO: 3768 - Homo  1 . . . 379 341/379 (89%) sapiens, 379 aa. [WO200058473-A2, 05 OCT. 2000] ABB90440 Human polypeptide SEQ ID NO  1 . . . 347 329/385 (85%) 0.0 2816 - Homo sapiens, 449 aa. 41 . . . 425 335/385 (86%) [WO200190304-A2, 29 NOV. 2001] ABP61860 Human polypeptide SEQ ID NO 214 - 96 . . . 358  263/263 (100%) e−148 Homo sapiens, 271 aa.  9 . . . 271  263/263 (100%) [US2002065394-A1, 30 MAY 2002] AAW73629 Human secreted protein clone 96 . . . 358  263/263 (100%) e−148 cd265_11 - Homo sapiens, 271 aa.  9 . . . 271  263/263 (100%) [WO9855614-A2, 10 DEC. 1998] ABB65708 Drosophila melanogaster polypeptide  1 . . . 342 126/386 (32%) 4e−48  SEQ ID NO 23916 - Drosophila 95 . . . 463 185/386 (47%) melanogaster, 484 aa. [WO200171042-A2, 27 SEP. 2001]

[0401] In a BLAST search of public sequence databases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D. TABLE 10D Public BLASTP Results for NOV10a Identities/ Protein Similarities for Accession NOV10a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value Q8WVT3 Similar to TPR-containing protein - 1 . . . 358 357/396 (90%) 0.0 Homo sapiens (Human), 735 aa. 340 . . . 735  358/396 (90%) Q8K2L8 Hypothetical protein - Mus 1 . . . 358 340/396 (85%) 0.0 musculus (Mouse), 797 aa. 402 . . . 797  351/396 (87%) Q8WVW1 CGI-87 protein - Homo sapiens 18 . . . 358  341/379 (89%) 0.0 (Human), 379 aa. 1 . . . 379 341/379 (89%) Q9Y395 CGI-87 protein - Homo sapiens 18 . . . 358  339/379 (89%) 0.0 (Human), 379 aa. 1 . . . 379 340/379 (89%) Q8N9N0 Hypothetical protein FLJ36862 - 1 . . . 278 276/322 (85%) e−149 Homo sapiens (Human), 696 aa. 323 . . . 644  277/322 (85%)

[0402] PFam analysis indicates that the NOV10a protein contains the domains shown in the Table 10E. TABLE 10E Domain Analysis of NOV10a Identities/ NOV10a Similarities for Pfam Match the Matched Expect Domain Region Region Value TPR 168 . . . 201 8/34 (24%) 0.0053 23/34 (68%) 

Example 11

[0403] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A. TABLE 11A NOV11 Sequence Analysis SEQ ID NO: 41              3462 bp NOV11 a, G ATGGGGCCAGAACGGACAGGGGCCGCGCCGCTGCCGCTGCTGCTGGTGTTAGCGCTCAGTCAA CG165676-01 DNA Sequence GGCATTTTAAATTGTTGTTTGGCCTACAATGTTGCTCTCCCAGAAGCAAAAATATTTTCCGGTC CTTCAAGTGAACAGTTTGGCTATGCAGTGCAGCAGTTTATAAATCCAAAAGGCAACTGGTTACT GGTTGGTTCACCCTGGAGTGGCTTTCCTGAGAACCGAATGGGAGATGTGTATAAATGTCCTGTT GACCTATCCACTGCCACATGTGAAAAACTAAATTTGCAAACTTCAACAAGCATTCCAAATGTTA CTGAGATGAAAACCAACATGAGCCTCGGCTTGATCCTCACCAGGAACATCGGAACTGGAGGTTT TCTCACATGTGGTCCTCTGTGGGCACAGCAATGTGGGAATCAGTATTACACAACGGGTGTGTGT TCTGACATCAGTCCTGATTTTCAGCTCTCAGCCAGCTTCTCACCTGCAACTCACCCCTGCCCTT CCCTCATAGATGTTGTGGTTGTCTGTGATGAATCAAATAGTATTTATCCTTGGGATGCAGTAAA GAATTTTTTGGAAAAATTTGTACAAGGCCTCGATATAGGCCCCACAAAGACACAGGTGGGGTTA ATTCAGTATGCCAATAATCCAAGAGTTGTGTTTAACTTGAACACATATAAAACCAAAGAAGAAA TCATTGTAGCAACATCCCAGACATCCCAATATGGTGGGGACCTCACAAACACATTCGGAGCAAT TCAATATGCAAGAAAATATGCTTATTCAGCAGCTTCTGGTGCGCGACGAAGTGCTACGAAAGTA ATGGTAGTTGTAACTGACGGTGAATCACATGATGGTTCAATGTTGAAAGCTGTGATTGATCAAT GCAACCATGACAATATACTGAGGTTTGGCATAGCAGTTCTTGGGTACTTAAACAGAAACGCCCT TCATACTAAAAATTTAATAAAAGAAATAAAAGCAATCGCTAGTATTCCAACAGAAAGATACTTT TTCAATGTGTCTGATGAAGCAGCTCTACTAGAAAAGGCTGGGACATTAGGAGAACAAATTTTCA GCATTGAAGGTACTGTTCAAGGACGAGACAACTTTCAGATGGAAATGTCACAAGTGGGATTCAG TGCAGATTACTCTTCTCAAAATGATATTCTGATGCTGGGTGCAGTGGGAGCTTTTGGCTGGAGT GGGACCATTGTCCAGAAGACATCTCATGGCCATTTGATCTTTCCTAAACAAGCCTTTGACCAAA TTCTGCAGGACAGAAATCACAGTTCATATTTAGGTTACTCTGTGGCTGCAATTTCTACTGGAGA AAGCACTCACTTTGTTGCTGGTGCTCCTCGGGCAAATTATACCGGCCAGATAGTGCTATATAGT GTGAATGAGAATGGCAATATCACGGTTATTCAGGCTCACCGAGGTGACCAGATTGGCTCCTATT TTGGTAGTGTGCTGTGTTCAGTTGATGTCGATAAAGACACCATTACAGACGTGCTCTTGGTAGG TGCACCAATGTACATGAGTGACCTAAAGAAAGAGGAAGGAAGAGTCTACCTGTTTACTATCAAA GAGGGCATTTTGGGTCAGCACCAATTTCTTGAAGGCCCCGAGGGCATTGAAAACACTCGATTTG GTTCAGCAATTGCAGCTCTTTCAGACATCAACATGGATGGCTTTAATGATGTGATTGTTGGTTC ACCACTAGAAAATCAGAATTCTGGAGCTGTATACATTTACAATGGTCATCAGGGCACTATCCGC ACAAAGTATTCCCAGAAAATCTTGGGATCCGATGGAGCCTTTAGCAGCCATCTCCAGTACTTTG GGAGGTCCTTGGATCGCTATCGAGATTTAAATGGGGATTCCATCACCGATGTGTCTATTGGTGC CTTTGGACAAGTCGTTCAACTCTGGTCACAAAGTATTGCTGATGTAGCTATAGAAGCTTCATTC ACACCAGAAAAAATCACTTTGGTCAACAAGAATGCTCAGATAATTCTCAAACTCTGCTTCAGTG CAAAGTTCAGACCTACTAAGCAAAACAATCAAGTGGCCATTGTATATAACATCACACTTGATGC AGATGGATTTTCATCCAGAGTAACCTCCAGCGGGTTATTTAAAGAAAACAATGAAAGGTGCCTG CAGAAGAATATGGTAGTAAATCAAGCACAGAGTTGCCCCGAGCACATCATTTATATACAGGAGC CCTCTGATGTTGTCAACTCTTTGGATTTGCGTGTCGACATCAGTCTGGAAAACCCTGGCACTAG CCCTGCCCTTGAAGCCTATTCTGAGACTGCCAACGTCTTCAGTATTCCTTTCCACAAAGACTGT GGTGAGGACGGACTTTGCATTTCTGATCTAGTCCTAGATGTCCGACAAATACCAGCTGCTCAAG AACAACCCTTTATTGTCAGCAACCAAAACAAAACGTTAACATTTTCAGTAACCCTGAAAAATAA AAGGGAAAGTCCATACAACACTCGAATTGTTGTTGATTTTTCAGAAAACTTGTTTTTTGCATCA TTCTCCCTGCCGGTTGATGGGACAGAAGTAACATGCCAGGTGGCTGCATCTCAGAAGTCTGTTG CCTGCGATGTAGGCTACCCTGCTTTAAAGACACAACAACAGGTGACTTTTACTATTAACTTTGA CTTCAATCTTCAAAACCTTCAGAATCAGGCGTCTCTCAGTTTCCAGGCCTTAAGTGAAAGCCAA GAAGAAAACAAGGCTGATAATTTGGTCAACCTCAAAATTCCTCTCCTGTATGATGCTGAAATTC ACTTAACAAAGGTAACAACAGGAAGTGTTCCAGTAACCATGGCAACTGTAATCATCCACATCCC TCAGTATACCAAAGAAAAGAACCCACTGATGTACCTAACTGGGGTGCAAACAGACAAGGCTGGT GACATCAGTTGTAATGCAGATATCAATCCACTGAAAATAGGACAAACATCTTCTTCTGTATCTT TCAAAAGTGAAAATTTCAGGCACACCAAAGAATTGAACTGCAGAACTGCTTCCTGTAGTAATGT TACCTGCTGGTTGAAAGACGTTCACATGAAAGGAGAATACTTTGTTAATGTGACTACCAGAATT TGGAACGGGACTTTCGCATCATCAACGTTCCAGACAGTACAGCTAACGGCAGCTGCAGAAATCA ACACCTATAACCCTGAGATATATGTGATTGAAGATAACACTGTTACGATTCCCCTGATGATAAT GAAACCTGATGAGAAAGCCGAAGTACCAACAGGAGTTATAATAGGAAGTATAATTGCTGGAATC CTTTTGCTGTTAGCTCTGGTTGCAATTTTATGGAAGCTCGGCTTCTTCAAAAGAAAATATGAAA AGATGACCAAAAATCCAGATGAGATTGATGAGACCACAGAGCTCAGTAGCTGA ACCAGCAGACC TACCTG ORF Start: ATG at 2                        ORF Stop: TGA at 3443 SEQ ID NO: 42              1147 aa         MW at 125495.9 kD NOV11a, MGPERTGAAPLPLLLVLALSQGILNCCLAYNVGLPEAKIFSGPSSEQFCYAVQQFINPKGNWLL CG165676-01 Protein Sequence VGSPWSGFPENRMGDVYKCPVDLSTATCEKLNLQTSTSIPNVTEMKTNMSLGLILTRNMGTGGF LTCGPLWAQQCGNQYYTTGVCSDISPDFQLSASFSPATQPCPSLIDVVVVCDESNSIYPWDAVK NFLEKFVQGLDIGPTKTQVGLIQYANNPRVVFNLNTYKTKEEMIVATSQTSQYGGDLTNTFGAI QYARKYAYSAASGGRRSATKVMVVVTDGESHDGSMLKAVIDQCNHDNILRFGIAVLGYLNRNAL DTKNLIKEIKAIASIPTERYFFNVSDEAALLEKAGTLGEQIESIEGTVQGGDNFQMEMSQVGFS ADYSSQNDILMLGAVGAFGWSGTIVQKTSHGHLIFPKQAFDQILQDRNHSSYLGYSVAAISTGE STHFVAGAPPANYTGQIVLYSVNENGNITVIQAHRGDQIGSYFGSVLCSVDVDKDTITDVLLVG APMYMSDLKKEEGRVYLFTIKEGILCQHQFLEGPEGIENTRFGSAIAALSDINMDGFNDVIVGS PLENQNSGAVYIYNGHQGTIRTKYSQKILGSDCAFRSHLQYFCRSLDGYGDLNGDSITDVSIOA FGQVVQLWSQSIADVAIEASFTPEKITLVNKNAQIILKLCFSAKFRPTKQNNQVAIVYNITLDA DGFSSRVTSRGLFKENNERCLQKNMVVNQAQSCPEHIIYIQEPSDVVNSLDLRVDISLENPGTS PALEAYSETAKVFSIPFHKDCGEDGLCISDLVLDVRQIPAAQEQPFIVSNQNKRLTFSVTLKNK RESAYNTGIVVDFSENLFFASFSLPVDGTTEVCQVAASQKSVACDVGYPALKREQQVTFTINFD FNLQNLQNQASLSFQALSESQEENKADNLVNLKIPLLYDAEIHLTKVTTGSVPVSMATVIIHIP QYTKEKNPLMYLTGVQTDKAGDISCNADINPLKIGQTSSSVSFKSENFRHTKELNCRTASCSNV TCWLKDVHNKGEYFVNVTTRIWNGTFASSTFQTVQLTAAAEINTYNPEIYVIEDNTVTIPLMIM KPDEKAEVPTGVIIGSIIAGILLLLALVAILWKLCFFKRKYEKMTKNPDEIDETTELSS

[0404] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B. TABLE 11B Protein Sequence Properties NOV11a SignalP Cleavage site between residues 30 and 31 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 5; pos. chg 1; neg. chg 1 H-region: length 30; peak value 9.82 PSG score: 5.42 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 1.12 possible cleavage site: between 22 and 23 >>> Seems to have a cleavable signal peptide (1 to 22) ALOM: Klein et al's method for TM region allocation Init position for calculation: 23 Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = −13.27 Transmembrane 1100-1116 PERIPHERAL Likelihood =    0.95 (at 943) ALOM score: −13.27 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 11 Charge difference: −2.0 C(−1.0)-N(1.0) N >= C: N-terminal side will be inside >>> membrane topology: type 1a (cytoplasmic tail 1117 to 1147) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment (75): 10.10 Hyd Moment (95): 5.95 G content:  4 D/E content: 2 S/T content:  2 Score: −6.90 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 15 ERT|GA NUCDISC: discrimination of nuclear localization signals pat 4: none pat 7: none bipartite: none content of basic residues: 7.7% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: GPER none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: 1128 Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 89 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 55.6%: endoplasmic reticulum 22.2%: Golgi 11.1%: plasma membrane 11.1%: extracellular, including cell wall >> indication for CG165676-01 is end (k = 9)

[0405] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11C. TABLE 11C Geneseq Results for NOV11a Identities/ Similarities for Geneseq Protein/Organism/Length NOV11a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value AAY07729 Armenian hamster alpha-2 integrin 1 . . . 1147 1139/1184 (96%) 0.0 subunit protein - Cricetulus 1 . . . 1183 1141/1184 (96%) migratorius, 1183 aa. [WO9916465-A1, 08 APR. 1999] AAW70542 Integrin alpha-2 chain - Homo 1 . . . 1098 1095/1132 (96%) 0.0 sapiens, 1367 aa. [WO9832771-A1, 1 . . . 1132 1097/1132 (96%) 30 JUL. 1998] ABG29239 Novel human diagnostic protein 206 . . . 1147   937/976 (96%) 0.0 #29230 - Homo sapiens, 979 aa. 4 . . . 979   940/976 (96%) [WO200175067-A2, 11 OCT. 2001] ABB90759 Human Tumour Endothelial Marker 23 . . . 1131   466/1182 (39%) 0.0 polypeptide SEQ ID NO 250 - Homo 22 . . . 1175   680/1182 (57%) sapiens, 1179 aa. [WO200210217-A2, 07 FEB. 2002] ABB90788 Rat Tumour Endothelial Marker 1 . . . 1131  471/1202 (39%) 0.0 polypeptide SEQ ID NO 307 - Rattus 1 . . . 1176  678/1202 (56%) sp., 1180 aa. [WO200210217-A2, 07 FEB. 2002]

[0406] In a BLAST search of public sequence databases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D. TABLE 11D Public BLASTP Results for NOV11a Identities/ Protein Similarities for Accession NOV11a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value AAM34795 Integrin, alpha 2 (CD49B, alpha 2 1 . . . 1147 1147/1181 (97%) 0.0 subunit of VLA-2 receptor) - Homo 1 . . . 1181 1147/1181 (97%) sapiens (Human), 1181 aa. P17301 Integrin alpha-2 precursor (Platelet 1 . . . 1147 1146/1181 (97%) 0.0 membrane glycoprotein Ia) (GPIa) 1 . . . 1181 1147/1181 (97%) (Collagen receptor) (VLA-2 alpha chain) (CD49b) - Homo sapiens (Human), 1181 aa. P53710 Integrin alpha-2 precursor (Platelet 12 . . . 1147   986/1170 (84%) 0.0 membrane glycoprotein Ia) (GPIa) 1 . . . 1170 1069/1170 (91%) (Collagen receptor) (VLA-2 alpha chain) (CD49b) - Bos taurus (Bovine), 1170 aa (fragment). Q62469 Integrin alpha-2 precursor (Platelet 1 . . . 1147  945/1181 (80%) 0.0 membrane glycoprotein Ia) (GPIa) 1 . . . 1178 1040/1181 (88%) (Collagen receptor) (VLA-2 alpha chain) (CD49b) - Mus musculus (Mouse), 1178 aa. O42094 ALPHA1 integrin - Gallus gallus 29 . . . 1131   456/1179 (38%) 0.0 (Chicken), 1171 aa. 17 . . . 1167   671/1179 (56%)

[0407] PFam analysis indicates that the NOV11a protein contains the domains shown in the Table 11E. TABLE 11E Domain Analysis of NOV11a Identities/ NOV11a Similarities for Pfam Match the Matched Expect Domain Region Region Value FG-GAP  45 . . . 103 16/65 (25%) 6.1e−05 38/65 (58%) vwa 174 . . . 357 71/208 (34%)  1.8e−63 155/208 (75%)  FG-GAP 434 . . . 486 16/64 (25%) 2.2e−06 38/64 (59%) FG-GAP 488 . . . 549 21/66 (32%) 4.7e−13 47/66 (71%) FG-GAP 551 . . . 610 24/67 (36%) 2.2e−17 53/67 (79%) FG-GAP 615 . . . 667 16/66 (24%)   5e−08 42/66 (64%) integrin_A 1121 . . . 1135  7/15 (47%) 0.0055 14/15 (93%)

Example 12

[0408] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A. TABLE 12A NOV12 Sequence Analysis SEQ ID NO: 43              1105 bp NOV12a, AGGAGGAAAAACAAGTGTGTGTTGGGGGGAACAGGGGGAAAAGCATTTTTGGTGGATGGT ATGA CG165719-04 DNA Sequence AGCCAGCCATGGAAACTGCACCCGAGGAAAATACTCAACAAAGCCAAGAGAGAAAAGTGAACAG CACAGCTGAAATGGAAATTGGCAGGTACCACTGGATGTACCCAGGCTCAAAGAACCACCAGTAC CATCCCGTGCCAACCCTGGGGGACAGGGCTAGCCCCTTCAGCAGTCCAGGCTGCTTTGAATGCT GCATCAAGTGTCTGGGACGAGTCCCCTACGCCTCCCTGGTGGCCACCATCCTCTGCTTCTCCGG GGTGGCCTTATTCTGCGGCTGTGGGCATGTGGCTCTCGCAGGCACCGTGGCGATTCTTGAGCAA CACTTCTCCACCAACGCCAGTGACCATGCCTTGCTGAGCGAGGTGATACAACTGATCCAGTATG TCATCTATGGAATTGCGTCCTTTTTCTTCTTGTATGGGATCATTCTGTTGGCAGAAGGCTTTTA CACCACAAGTGCAGTGAAAGAACTGCACGGTGAGTTTAAAACAACCGCTTGTGGCCGATGCATC AGTGGAATGTTCGTTTTCCTCACCTATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCT CAGCGGTGCCCGTGTTTATGTTCTACAACATATGGTCAACTTGTGAAGTCATCAAGTCACCGCA GACCAACGGGACCACGGCTGTGGAGCAGATCTGTGTGGATATCCGACAATACGGTATCATTCCT TGGAATGCTTTCCCCGGAAAAATATGTGGCTCTGCCCTGGAGAACATCTGCAACACAAACGAGT TCTACATGTCCTATCACCTGTTCATTGTGGCCTGTGCAGGAGCTGGTGCCACCGTCATTGCCCT GATCCACTTCCTCATGATACTGTCTTCTGACTGGGCTTACTTAAAGGATGCGAGCAAAATGCAG GCTTACCAGGATATCAAAGCAAAGGAAGAACAGGAACTGCAAGATATCCAGTCTCCGTCAAAAG AACAACTCAATTCTTACACATAA ATGTTTGCCAGAGTGTTTCGGCCGACGTATTTACAGCTCTG ACAAATCATCAGACAGC ORF Start: ATG at 61                       ORF Stop: TAA at 1045 SEQ ID NO: 44               328 aa         MW at 36219.3 kD NOV12a, MKPAMETAAEENTEQSQERKVNSRAEMEIGRYMWMYPGSKNHQYHPVPTLGDRASPLSSPGCFE CG165719-04 Protein Sequence CCIKCLGGVPYASLVATILCFSGVALFCGCGHVALAGTVAILEQHFSTNASDHALLSEVIQLMQ YVIYGIASFFFLYGIILLAEGFYTTSAVKELHGEFKTTACGRCISGMFVFLTYVLGVAWLGVFG FSAVPVFMFYNIWSTCEVIKSPQTNGTTGVEQICVDIRQYGIIPWNAFPGKICGSALENICNTN EFYMSYHLFIVACAGAGATVIALIHFLMILSSNWAYLKDASKMQAYQDIKAKEEQELQDIQSRS KEQLNSYT SEQ ID NO: 45              1133 bp NOV12b, ACGAGGAAAAACAAGTGTGTGTTGGGGGGAACACGGCGAAAAGCATTTTTGGTGGATGGT ATGA CG165719-02 DNA Sequence AGCCAGCCATCGAAACTGCAGCCGAGGAAAATACTGAAGAAAGCCAAGAGAGAAAAGTGAACAG CAGAGCTGAAATGGAAATTGGCAGGTACCACTGGATGTACCCAGGCTCAAAGAACCACCAGTAC GCATCAAGTGTCTGGGAGGAGTCCCCTACGCCTCCCTGGTCGCCACCATCCTCTGCTTCTCCGG CATCCCCTGCCAACCCTGGGGGACAGGGCTAGCCCCTTGAGCAGTCCAGGCTGCTTTGAATGCT GGTGGCCTTATTCTGCGGCTGTGGGCATGTCGCTCTCGCAGGCACCGTGCCGATTCTTGAGCAA CACTTCTCCACCAACGCCAGTGACCATGCCTTGCTGAGCCACGTGATACAACTGATGCAGTATG TCATCTATGGAATTGCGTCCTTTTTCTTCTTGTATGGGATCATTCTGTTGGCAGAAGGCTTTTA CACCACAAGTGCAGTGAAAGAACTGCACGGTGAGTTTAAAACAACCGCTTGTGGCCGATGCATC AGTGGAATGTTCGTTTTCCTCACCTATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCT CAGCGGTGCCCGTGTTTATGTTCTACAACATATGGTCAACTTGTGAAGTCATCAAGTCACCGCA GACCAACGGGACCACGGGTGTGGAGCAGATCTGTGTGGATATCCGACAATACGGTATCATTCCT TGGAATGCTTTCCCCGGAAAAATATGTGGCTCTGCCCTGGAGAACATCTGCAACACAAACGAGT TCTACATGTCCTATCACCTGTTCATTGTGGCCTGTGCAGGAGCTGGTGCCACCGTCATTGCCCT GCTGATCTACATGATGGCTACTACATATAACTATGCGGTTTTGAAGTTTAAGAGTCGGGAAGAT TGCTGCACTAAATTCTAA ATTGCATAAGGAGTTTTAGAGAGCTATGCTCTGTAGCATGAAATAT CACTGACACTCCAGACTAAAGCAGAGTCTAGGTTTCTGCAATTTGTTACAGTAATTTGTAATAG CTTTGTAACTCACCTGCATGTAGATAATAAGATGACTACTGTACA ORF Start: ATG at 61                       ORF Stop: TAA at 976 SEQ ID NO: 46               305 aa         MW at 33537.5 kD NOV12b, MKPAMETAAEENTEQSQERKVNSRAEMEIGRYHWMYPGSKNHQYHPVPTLGDRASPLSSPGCFE CG165719-02 Protein Sequence CCIKCLGGVPYASLVATILCFSGVALFCGCGHVALAGTVAILEQHFSTNASDHALLSEVIQLMQ YVIYGIASFFFLYGIILLAEGFYTTSAVKELHGEFKTTACGRCISGMFVFLTYVLGVAWLGVFG FSAVPVFMFYNIWSTCEVIKSPQTNGTTGVEQICVDIRQYGIIPWNAFPGKICGSALENICNTN EFYMSYHLFIVACAGAGATVIALLIYMMATTYNYAVLKPKSREDCCTKP SEQ ID NO: 47              1182 bp NOV12c, AGGAGGAAAAACAAGTGTGTGTTGGGGGGAACAGGGGGAAAAGCATTTTTGGTGGATGGT ATGA CG165719-03 DNA Sequence AGCCAGCCATGGAAACTGCAGCCGAGGAAAATACTGAACAAAGCCAAGAGAGAAAAGGCTGCTT TGAATGCTGCATCAAGTGTCTGGGAGGAGTCCCCTACGCCTCCCTGGTGGCCACCATCCTCTGC TTCTCCGGGGTGGCCTTATTCTGCGGCTGTGGGCATGTGGCTCTCGCAGGCACCGTGGCGATTC TTGAGCAACACTTCTCCACCAACGCCAGTGACCATGCCTTGCTGAGCGAGGTGATACAACTGAT GCAGTATGTCATCTATGGAATTGCGTCCTTTTTCTTCTTGTATGGGATCATTCTGTTGGCAGAA GGCTTTTACACCACAAGTGCAGTGAAAGAACTGCACGGTGAGTTTAAAACAACCGCTTGTGGCC GATGCATCAGTGGAATGTTCGTTTTCCTCACCTATGTGCTTGGAGTGGCCTGGCTGGGTGTGTT TGGTTTCTCAGCGGTGCCCGTGTTTATGTTCTACAACATATGGTCAACTTGTGAAGTCATCAAG TCACCGCAGACCAACGGGACCACGGGTGTGGAGCAGATGCTGTGTGGATACCGACAATACGGTA TCATTCCTTGGAATGCTTTCCCCCGGAAAAATATGGCTCTGCCCTGGAGAACATCTGCAACAAC AAACGAGTTCTACATGTCCTATCACCTGTTCATTGTGGCCTGTGCAGGAGCTGGTGCCACCGTC ATTGCCCTGATCCACTTCCTCATGATACTGTCTTCTAACTGGGCTTACTTAAAGGATGCGAGCA AAATGCAGGCTTACCAGGATATCAAAGCAAAGGAAGAACAGGAACTGCAAGATATCCAGTCTCG GTCAAAAGAACAACTCAATTCTTACACATAA ATGTTTGCCAGAGTGTTTCGGCCGACGTATTTA CAGCTCTGACAAATCATCAGACAGCTGCTCTGCAGTACAGATGTGTATCCCACCAAACTAATGT AGATGTACAAACACTTCACTGTCTGTCTCAAGCTGCTGGGATGTATCTCTAGGAAAACCTTCCA GTGGGTAAATCTTTTTCTTTAGAACAAATATTGGAGGTTCATGTTGCCCCATTTAAAGGGCACA CTTTTACAAATGATCGTCATACTTTGGGAT ORF Start: ATG at 61                       ORF Stop: TAA at 925 SEQ ID NO: 48               288 aa         MW at 31670.3 kD NOV12c, MKPAMETAAEENTEQSQERKGCFECCIKCLGGVPYASLVATILCFSGVALFCGCGHVALAGTVA CG165719-03 Protein Sequence ILEQHFSTNASDHALLSEVIQLMQYVIYGIASFFFLYGIILLAEGFYTTSAVKELHGEFKTTAC GRCISGMFVFLTYVLGVAWLGVFGFSAVPVFMFYNIWSTCEVIKSPQTNGTTGVEQICVDIRQY GIIPWNAFPGKICGSALENICNTNEFYMSYHLFIVACAGAGATVIALIHFLMILSSNWAYLKDA SKMQAYQDIKAKEEQELQDIQSRSKEQLNSYT SEQ ID NO: 49              1302 bp NOV12d, AGGAGGAAAAACAAGTGTGTGTTGGGGGGAACAGGGGGAAAAGCATTTTTGGTGGATGGT ATGA CG165719-01 DNA Sequence AGCCAGCCATGGAAACTGCAGCCGAGGAAAATACTGAACAAAGCCAAGAGAGAAAAGTGAACAG CAGAGCTGAAATGGAAATTCGCAGGTACCACTGGATGTACCCAGGCTCAAAGAACCACCAGTAC CATCCCGTGCCAACCCTGGGGGACAGGGCTAGCCCCTTGAGCAGTCCAGCCTGCTTTGAATGCT GCATCAAGTGTCTGGGAGGAGTCCCCTACGCCTCCCTGGTGGCCACCATCCTCTGCTTCTCCGG GGTGGCCTTATTCTGCGGCTGTGGGCATGTGGCTCTCGCAGGCACCGTGCCGATTCTTGAGCAA CACTTCTCCACCAACGCCAGTGACCATGCCTTGCTGAGCGAGGTGATACAACTGATGCAGTATG TCATCTATGGAATTGCGTCCTTTTTCTTCTTGTATGGGATCATTCTGTTGGCAGAAGGCTTTTA CACCACAAGTGCACTGAAAGAACTGCACGGTCAGTTTAAAACAACCGCTTGTGGCCGATGCATC AGTCGAATGTTCGTTTTCCTCACCTATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCT CAGCGGTGCCCGTGTTTATGTTCTACAACATATGGTCAACTTGTGAAGTCATCAAGTCACCGCA GACCAACGGGACCACGGGTGTGGAGCAGATCTGTGTGGATATCCGACAATACGGTATCATTCCT TGGAATGCTTTCCCCGGAAAAATATGTOGCTCTGCCCTGGAGAACATCTGCAACACAAACGAGT TCTACATGTCCTATCACCTGTTCATTGTGGCCTGTGCAGGAGCTGGTGCCACCGTCATTGCCCT GATCCACTTCCTCATGATACTGTCTTCTAACTGGGCTTACTTAAAGGATGCGAGCAAAATGCAG GCTTACCAGGATATCAAAGCAAAGGAAGAACAGGAACTGCAAGATATCCAGTCTCCGTCAAAAG AACAACTCAATTCTTACACATAA ATGTTTGCCAGAGTGTTTCGGCCGACGTATTTACAGCTCTG ACAAATCATCAGACAGCTGCTCTGCAGTACAGATGTGTATCCCACCAAACTAATGTAGATGTAC AAACACTTCACTGTCTGTCTCAAGCTGCTQGGATGTATCTCTAGGAAAACCTTCCAGTGGGTAA ATCTTTTTCTTTAGAACAAATATTGCAGGTTCATGTTGCCCCATTTAAAGGGCACACTTTTACA AATGATCGTCATACTTTGGGAT ORF Start: ATG at 61                       ORF Stop: TAA at 1045 SEQ ID NO: 50               328 aa         MW at 36219.3 kD NOV12d, MKPAMETAAEENTEQSQERKVNSRAEMEIGRYHWMYPGSKNHQYHPVPTLGDRASPLSSPGCFE CG165719-01 Protein Sequence CCIKCLGGVPYASLVATILCFSGVALFCGCGHVALAGTVAILEQHFSTNASDHALLSEVIQLMQ YVIYGIASFFFLYGIILLAEGFYTTSAVKELHGEFKTTACGRCISGMFVFLTYVLGVAWLGVFG FSAVPVFMFYNIWSTCEVIKSPQTNGTTGVEQICVDIRQYGIIPWNAFPGKICQSALENICNTD EFYMSYHLFIVACAGAGATVIALIHFLNHLSSNWAYLKDASKHQAYQDIKAKEEQELQDIQSRS KEQLNSYT SEQ ID NO: 51               929 bp NOV12e, AGGAGGAAAAACAAGTGTGTGTTGGGGGGAACAGGGGGAAAAGCATTTTTCGTGGATGGT ATGA CG165719-05 DNA Sequence AGCCAGCCATGGAAACTGCAGCCGAGGAAAATACTGAACAAAGCCAAGAGAGAAAAGGCTGCTT TGAATGCTGCATCAAGTGTCTGGGAGGAGTCCCCTACGCCTCCCTGGTGGCCACCATCCTCTGC TTCTCCGGGGTGGCCTTATTCTGCGGCTGTCGGCATGTGGCTCTCGCAGCCACCGTGGCGATTC TTGAGCAACACTTCTCCACCAACGCCAGTGACCATGCCTTGCTGAGCGAGGTGATACAACTGAT GCAGTATGTCATCTATGGAATTGCGTCCTTTTTCTTCTTGTATGGGATCATTCTGTTGGCAGAA GGCTTTTACACCACAAGTGCAGTGAAAGAACTGCACGGTGAGTTTAAAACAACCGCTTGTGGCC GATGCATCAGTGGAATGTTCGTTTTCCTCACCTATGTGCTTCGAGTGGCCTGGCTCGGTGTGTT TGGTTTCTCAGCGGTGCCCGTGTTTATGTTCTACAACATATGGTCAACTTGTGAAGTCATCAAG TCACCGCACACCAACGGGACCACGGGTGTGGAGCAGATCTGTGTGGATATCCGACAATACGGTA TCATTCCTTGGAATGCTTTCCCCCGAAAAATATGTGGCTCTGCCCTGGAGAACATCTGCAACAC AAACGAGTTCTACATGTCCTATCACCTGTTCATTQTGGCCTGTGCAGGAGCTGGTGCCACCGTC ATTGCCCTGCTGATCTACATGATGGCTACTACATATAACTATGCGGTTTTGAAGTTTAAGAGTC GGGAAGATTGCTGCACTAAATTCTAA ATTGCATAAGGAGTTTTAGAGAGCTATGCTCTGTAGCA TGAAATATCACTGACACTCCAGAAAGGGCGATT ORF Start: ATG at 61                       ORF Stop: TAA at 856 SEQ ID NO: 52               265 aa         MW at 28988.5 kD NOV12e, MKPAMETAAEENTEQSQERKGCFECCIKCLGGVPYASLVATILCFSGVALFCGCGHVALAGTVA CG165719-05 Protein Sequence ILEQHFSTNASDHALLSEVIQLMQYVIYGIASFFFLYGILLAQEGFYTTSAVKELHGEFKTTAC GRCISGMFVFLTYVLGVAWLGVFGFSAVPVFMFYNIWSTCEVIKSPQTNGTTGVEQICVDIRQY GIIPWNAPPGKICGSALENICNTNEFYMSYHLFIVACAGAGATVIALLIYMMATTYNYAVLKFK SREDCCTKF

[0409] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 12B. TABLE 12B Comparison of NOV12a against NOV12b through NOV12e. Identities/ Similarities for Protein NOV12a Residues/ the Matched Sequence Match Residues Region NOV12b 1 . . . 298 285/298 (95%) 1 . . . 298 291/298 (97%) NOV12c 1 . . . 328 288/328 (87%) 1 . . . 288 288/328 (87%) NOV12d 1 . . . 328  328/328 (100%) 1 . . . 328  328/328 (100%) NOV12e 1 . . . 298 245/298 (82%) 1 . . . 258 251/298 (84%)

[0410] Further analysis of the NOV12a protein yielded the following properties shown in Table 12C. TABLE 12C Protein Sequence Properties NOV12a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 11; pos. chg 1; neg. chg 3 H-region: length 2; peak value 0.00 PSG score: −4.40 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −10.13 possible cleavage site: between 60 and 61 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 4 INTEGRAL Likelihood = −6.26 Transmembrane  78-94 INTEGRAL Likelihood = −6.74 Transmembrane 130-146 INTEGRAL Likelihood = −5.15 Transmembrane 175-191 INTEGRAL Likelihood = −8.17 Transmembrane 264-280 PERIPHERAL Likelihood =   3.07 (at 195) ALOM score: −8.17 (number of TMSs: 4) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 85 Charge difference: 0.0 C(0.0)-N(0.0) N >= C: N-terminal side will be inside >>> membrane topology: type 3a MITDISC: discrimination of mitochondrial targeting seq R content:  0 Hyd Moment(75): 7.96 Hyd Moment(95): 11.32 G content: 0 D/E content:  2 S/T content: 1 Score: −5.88 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 6.1% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions 290 A 0.60 291 Y 0.75 292 L 0.75 293 K 0.88 294 D 0.93 295 A 0.98 296 S 0.99 297 K 1.00 298 M 1.00 299 Q 1.00 300 A 1.00 301 Y 1.00 302 Q 1.00 303 D 1.00 304 I 1.00 305 K 1.00 306 A 1.00 307 K 1.00 308 E 1.00 309 E 1.00 310 Q 1.00 311 E 1.00 312 L 1.00 313 Q 1.00 314 D 1.00 315 I 1.00 316 Q 1.00 317 S 1.00 318 R 1.00 319 S 1.00 320 K 1.00 321 E 1.00 322 Q 1.00 323 L 1.00 324 N 1.00 325 S 0.97 326 Y 0.96 327 T 0.87 total: 38 residues Final Results (k = 9/23): 55.6%: endoplasmic reticulum 44.4%: mitochondrial >> indication for CG165719-04 is end (k = 9)

[0411] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12D. TABLE 12D Geneseq Results for NOV12a Identities/ Similarities for Geneseq Protein/Organism/Length NOV12a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value ABG70364 Novel human thrombopoietin variant 27 . . . 298 259/272 (95%)  e−155 protein, NV-23 - Homo sapiens, 279  1 . . . 272 265/272 (97%) aa. [US2002068342-A1, 06 JUN. 2002] AAY09510 Human M6b1 protein - Homo sapiens,  1 . . . 298 245/298 (82%)  e−138 265 aa. [WO9921982-A1,  1 . . . 258 251/298 (84%) 06 MAY 1999] AAW39215 Human M6 protein - Homo sapiens, 61 . . . 328 155/276 (56%) 2e−86 278 aa. [JP10014577-A, 20 JAN. 1998] 13 . . . 278 209/276 (75%) ABG02005 Novel human diagnostic 49 . . . 294 134/246 (54%) 1e−76 protein #1996 - Homo sapiens, 289 . . . 533  173/246 (69%) 541 aa. [WO200175067-A2, 11 OCT. 2001] AAR95171 Murine CNS myelin membrane 61 . . . 294 130/234 (55%) 8e−76 proteolipid protein isoform DM20 -  2 . . . 234 169/234 (71%) Mus musculus, 242 aa. [EP685558-A1, 06 DEC. 1995]

[0412] In a BLAST search of public sequence databases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12E. TABLE 12E Public BLASTP Results for NOV11a Identities/ Protein Similarities for Accession NOV12a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value Q8N956 Hypothetical protein FLJ38338 - 1 . . . 328  328/328 (100%) 0.0 Homo sapiens (Human), 328 aa. 1 . . . 328  328/328 (100%) Q9JI65 Neuronal membrane glycoprotein 1 . . . 328 321/328 (97%) 0.0 M6-B - Mus musculus (Mouse), 328 1 . . . 328 324/328 (97%) aa. P35803 Neuronal membrane glycoprotein 1 . . . 328 284/328 (86%) e−162 M6-b (M6b) - Mus musculus 1 . . . 288 287/328 (86%) (Mouse), 288 aa. Q98ST3 Myelin PLP-related membrane 61 . . . 328  237/268 (88%) e−141 protein DM gamma1 - Xenopus 2 . . . 269 250/268 (92%) laevis (African clawed frog), 269 aa. Q8UUS8 DMgamma2 - Brachydanio rerio 61 . . . 328  218/268 (81%) e−132 (Zebrafish) (Danio rerio), 268 aa. 2 . . . 265 244/268 (90%)

[0413] PFam analysis indicates that the NOV12a protein contains the domains shown in the Table 12F. TABLE 12F Domain Analysis of NOV12a Identities/ NOV12a Similarities for Pfam Match the Matched Expect Domain Region Region Value Myelin_PLP 61 . . . 305 175/288 (61%) 2.3e−196 243/288 (84%)

Example 13

[0414] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A. TABLE 13A NOV13 Sequence Analysis SEQ ID NO: 53              1201 bp NOV13a, TTTGATCTGAAGACTAGGGGACA ATGGATATCATAGAGACAGCAAAACTTGAAGAACATTTGGA CG167488-02 DNA Sequence AAATCAACCCAGTGATCCTACGAACACTTATGCAAGACCCGCTGAACCTGTTGAAGAAGAAAAC AAAATGGCAATGGTAAACCCAAGAGCTTATCCAGTCGGGCTGCGAAAAGGCACCAAAAAGTACC CGGACTATATCCAAATTGCTATGCCCACTGAATCAAGGAACAAATTTCCACTAGAGTGGTGGAA AACGGGCATTGCCTTCATATATGCAGTTTTCAACCTCGTCTTGACAACCGTCATGATCACAGTT GTACATGAGACGGTCCCTCCCAAGAGCTTAGCCCTCCACTCCCAGACAAGTTTTTTTGATTACA TTGATAGGGTGAAATGGGCATTTTCTGTATCAGAAATAAATGGGATTATATTAGTTGGATTATG GATCACCCAGTGGCTGTTTCTGAGATACAAGTCAATAGTGGGACGCAGATTCTGTTTTATTATT GGAACTTTATACCTGTATCGCTGCATTACAATGTATGTTACTACTCTACCTGTGCCTGGAATGC ATTTCCAGTGTGCTCCAAAGCTCAATCGAGACTCTCAGGCAAAAGTTCAACGGATTCTACGATT GATTTCTGGTGGTGGATTGTCCATAACTCGATCACATATCTTATGTGGAGACTTCCTCTTCAGC GGTCACACGGTTACGCTGACACTGACTTATTTGTTCATCAAAGAATATTCGCCTCGTCACTTCT GGTGGTATCATTTAATCTGCTGGCTGCTGAGTGCTGCCGGGATCATCTGCATTCTTGTAGCACA CGAACACTACACTATCGATGTGATCATTGCTTATTATATCACAACACGACTGTTTTGGTGGTAC CATTCAATGGCCAATGAAAAGAACTTGAAGGTCTCTTCACAGACTAATTTCTTATCTCGAGCAT GGTGGTTCCCCATCTTTTATTTTTTTTGAGAAAAAGTACAAGGCTCAATTCCTTGCTGCTTCTC CTGGCCGCTGTCTTGGCCTCCTGGCTGCTTCAAATCATCATGCAAAAAGTATTCACGGGTTCAG AAGATTGGTGAAGACAATGAGAAATCGACCTGA GGAGCAAAACAAAGGCATCAGCTCTTACACC AAAAGAGTTAACGCTGTAACCAAAGAAGCGCGATTCCAGCACACTGCGC ORF Start: ATG at 24                       ORF Stop: TGA at 1119 SEQ ID NO: 54               365 aa         MW at 42279.7 kD NOV13a, MDIIETAKLEEHLENQPSDPTNTYARPAEPVEEENKNGNGKPKSLSSGLRKGTKKYPDYIQIAM CG167488-02 Protein Sequence PTESRNKFPLEWWKTGTAFIYAVFNLVLTTVMITVVHERVPPKELSPPLPDKFFDYIDRVKWAF SVSEINGIILVGLWITQWLFLRYKSIVGRRFCFIIGTLYLYRCITMYVTTLPVPGMHFQCAPKL NGDSQAKVQRILRLISGGGLSITGSHILCGDFLFSGHTVTLTLTYLFIKEYSPRHFWWYHLICW LLSAAGIICILVAHEHYTIDVIIAYYITTRLFWWYHSMANEKNLKVSSQTNFLSRAWWFPIFYF FEKNVQGSIPCCFSWPLSWPPGCFKSSCKKYSRVQKIGEDNEKST SEQ ID NO: 55              1893 bp NOV13b, CGGAGCTACCTTATAAAGACCATCTGTACATCCACTGTGAAATGGAGTTTCAAAATCACAAGCT CG167488-01 DNA Sequence TCTTTCCCACATGAACATAAGACTAGGAGCACATATGGAAGAGTAAAGTTGAAGGGAATTTGGA TGATGATTTGGCAAGATGCTGTGGGATAGTAACATCTTTTTGAGGGAAGAATTGGCTTCCTTTC TTGAAAGTGGTGAAGGTACAGCATATAGCTGCATGGAAGAAACAGTAATCGGATGGCTACCTTC TACATTTTGTATTAGGAAACAAAGTCCATTGTAAGAGTCCATGTTGATCTTGGAAATAGAAGGA TTGAAAAAAGCTAAATTTCCACAAAGAACAAGAACTTGACCATCTCCTTTTTGATCTGAAGACT AGGGGACAATGGATATCATAGAGACAGCAAAACTTGAAGAACATTTGGAAAATCAACCCAGTGA TCCTACGAACACTT ATGCAAGACCCGCTGAACCTGTTGAAGAAGAAAACAAAAATGGCAATTGG TAAACCCAAGAGCTTATCCAGTGGGCTGCGAAAAGGCACCAAAAAGTACCCGGACTATATCCAA ATTGCTATGCCCACTGAATCAAGGAACAAATTTCCACTAGAGTGGTGGAAAACGGGCATTGCCT TCATATATGCAGTTTTCAACCTCGTCTTGACAACCGTCATGATCACAGTTGTACATGAGAGGGT CCCTCCGAGGAGCTTAGCCCTCCACTCCCAGACAGTTTTTTTGATTACATTGATAGGGGTGAAA TGGGCATTTTCTGTATCAGAAATAAATGGGATTATATTAGTTGGATTATGGATCACCCAGTGGC TGTTTCTGAGATACAAGTCAATAGTCGGACGCAGATTCTGTTTTATTATTGGAACTTTATACCT GTATCGCTGCATTACAATGTATGTTACTACTCTACCTGTGCCTGGAATCCATTTCCAGTGTGCT CCAAAGCTCAATGGAGACTCTCAGGCAAAAGTTCAACGGATTCTACGATTGATTTCTGGTGGTG GATTGTCCATAACTGGATCACATATCTTATGTGGAGACTTCCTCTTCAGCGGTCACACGGTTAC GCTGACACTGACTTATTTGTTCATCAAAGAAGATTCGCCTCGTCACTTCTGGTGGTATCATTTA ATCTGCTGGCTGCTGAGTGCTGCCGGGATCATCTGCATTCTTGTAGCACACGAACACTACACTA TCGATGTGATCATTGCTTATTATATCACAACACCACTGTTTTCGTGGTACCATTCAATGGCCAA TGAAAAGAACTTGAAGGTCTCTTCACAGACTAATTTCTTATCTCGAGCATGGTGGTTCCCCATC TTTTATTTTTTTGAGAAAAATGTACAAGGCTCAATTCCTTGCTGCTTCTCCTGGCCGCTGTCTT GGCCTCCTGGCTGCTTCAAATCATCATGCAAAAAGTATTCACGGGTTCAGAAGATTGGTGAAGA CAATGAGAAATCGACCTGA GGAGCAAAACAAAGGCATCAGCTCTTACACCAAAAGAGTTAACGC TGTAACCAAAGGTATAGTTTTGTTTTTTATTTTAGGAGAACTGACTGGTAAATGAAGAAATGGA CCAAATTTTGTGTAAACGATTAGAAAGATGAACAAAGTATTGCCCTTTGACTCTTTTTCTTCTT CATCCTGAGAAAGATACATTCTCTTGCAGCTCTTCATTCATTGGTGACAAGCCCCCACCCCGGG ACTTTACTAATGAGCTTGTTAAAGAGGTGCCAAAGAACATATTCCTCCTTTCTTTATTCTTTCT CCACCAAAACCCTCTACTTCAGAATTTTTTCAGGATATTTTTCAGCCCAACGTCAGAAGAATGT GTTAATATTTTAAATAAAATATCTGGACATCTACAAA ORF Start: ATG at 463                      ORF Stop: TGA at 1489 SEQ ID NO: 56               342 aa         MW at 39679.3 kD NOV13b, MQDPLNLLKKKTKMAIGKPKSLSSGLRKGTKKYPDYIQIAMPTESRNKFPLEWWKTGIAFIYAV CG167488-01 Protein Sequence FNLVLTTVMITVVHERVPPKELSPPLPDKFFDYIDRVKWAFSVSEINGIILVGLWITQWLFLRY KSIVGRRFCFIIGTLYLYRCITMYVTTLPVPGMHFQCAPKLNGDSQAKVQRILRLISGGGLSIT GSHILCGDFLFSGHTVTLTLTYLFIKEDSPRHFWWYHLICWLLSAAGIICILVAHEHYTIDVII AYYITTRLFWWYHSMANEKDLKVSSQTNFLSRAWWFPIFYFFEKNVQGSIPCCFSWPLSWPPGC FKSSCKKYSRVQKIGEDNEKST

[0415] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 13B. TABLE 13B Comparison of NOV13a against NOV13b. Identities/ Similarities for Protein NOV13a Residues/ the Matched Sequence Match Residues Region NOV13b 27 . . . 365 327/339 (96%)  4 . . . 342 331/339 (97%)

[0416] Further analysis of the NOV13a protein yielded the following properties shown in Table 13C. TABLE 13C Protein Sequence Properties NOV13a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 11; pos. chg 1; neg. chg 4 H-region: length 2; peak value 0.00 PSG score: −4.40 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −13.01 possible cleavage site: between 25 and 26 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 3 INTEGRAL Likelihood = −6.21 Transmembrane  81-97 INTEGRAL Likelihood = −1.59 Transmembrane 133-149 INTEGRAL Likelihood = −9.98 Transmembrane 253-269 PERIPHERAL Likelihood =   1.11 (at 160) ALOM score: −9.98 (number of TMSs: 3) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 88 Charge difference: −1.5 C(−0.5)-N(1.0) N >= C: N-terminal side will be inside >>> membrane topology: type 3a MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 4.36 Hyd Moment(95): 8.65 G content: 0 D/E content: 2 S/T content: 0 Score: −6.99 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat 4: none pat 7: none bipartite: none content of basic residues: 10.7% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: KKXX-like motif in the C-terminus: NEKS SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 55.6%: endoplasmic reticulum 33.3%: mitochondrial 11.1%: vesicles of secretory system >> indication for CG167488-02 is end (k = 9)

[0417] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13D. TABLE 13D Geneseq Results for NOV13a Identities/ Similarities for Geneseq Protein/Organism/Length NOV13a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value ABB09578 Human cytochrome constitutive protein 1 . . . 354 215/354 (60%) e−130 45 - Homo sapiens, 413 aa. 61 . . . 409  272/354 (76%) [CN1333280-A, 30 JAN. 2002] AAM41726 Human polypeptide SEQ ID NO 6657 - 1 . . . 354 215/354 (60%) e−130 Homo sapiens, 430 aa. 78 . . . 426  272/354 (76%) [WO200153312-A1, 26 JUL. 2001] AAM39940 Human polypeptide SEQ ID NO 3085 - 1 . . . 354 215/354 (60%) e−130 Homo sapiens, 413 aa. 61 . . . 409  272/354 (76%) [WO200153312-A1, 26 JUL. 2001] AAG81320 Human AFP protein sequence SEQ ID 136 . . . 354  150/219 (68%) 2e−93  NO: 158 - Homo sapiens, 222 aa. 1 . . . 218 181/219 (82%) [WO200129221-A2, 26 APR. 2001] ABB60637 Drosophila melanogaster polypeptide 97 . . . 330  107/244 (43%) 5e−57  SEQ ID NO 8703 - Drosophila 1 . . . 240 155/244 (62%) melanogaster, 384 aa. [WO200171042-A2, 27 SEP. 2001]

[0418] In a BLAST search of public sequence databases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E. TABLE 13E Public BLASTP Results for NOV13a Identities/ Protein Similarities for Accession NOV13a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value Q8NHU3 Similar to putative - Homo sapiens 1 . . . 365  365/365 (100%) 0.0 (Human), 365 aa. 1 . . . 365  365/365 (100%) Q9D4B1 4933405A16Rik protein - Mus 96 . . . 365  260/270 (96%) e−162 musculus (Mouse), 270 aa. 1 . . . 270 267/270 (98%) Q8VCQ6 Hypothetical 48.7 kDa protein - 1 . . . 354 216/354 (61%) e−131 Mus musculus (Mouse), 413 aa. 61 . . . 409  274/354 (77%) CAC38570 Sequence 157 from Patent 136 . . . 354  150/219 (68%) 6e−93  WO0129221 - Homo sapiens 1 . . . 218 181/219 (82%) (Human), 222 aa. Q9DA37 1700010P07Rik protein - Mus 68 . . . 340  123/273 (45%) 2e−69  musculus (Mouse), 478 aa. 204 . . . 470  178/273 (65%)

Example 14

[0419] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A. TABLE 14A NOV14 Sequence Analysis SEQ ID NO: 57              1785 bp NOV14a, GTCGCCAGCTGAGGCGGTTTGTAAGTTTTGGGTCGCAGTATGCTAGAATTTTGAGGCTCCCTTC CG173318-01 DNA Sequence TGATGAAAATTGAGCTGTCCATGCAGCCATGGAACCCGGGTTACAGCAGTGAGGGGGCCACGGC TCAAGAAACTTACACATGTCCAAAAATGATTGAGATGGAGCAGGCGGAGGCCCAGCTTGCTGAG TTAGACCTGCTAGCCAGTATGTTCCCTGGTGAGAATGAGCTCATAGTGAATGACCAGCTGGCTG TAGCAGAACTGAAAGATTGTATTGAAAAGAAGACAATGGAGGGGCGATCTTCAAAAGTCTACTT TACTATCAATATGAACCTGGATGTATCTGACGAAAAAATCGTAATTCAGTTTTGCTTTTAGAGG GATTGAAAC ATGTTGAGACTTAAAACATTGGTTAGTGCACTTTTTCTTCTTCTCTTTAATCAGG CGATGTTTTCTCTGGCCTGTATTCTTCCCTTTAAATACCCGGCAGTTCTGCCTGAAATTACTGT CAGATCAGTATTATTGAGTACATCCCAGCAGACTCAGCTGAACACAGATCTGACTGCATTCCTG CAAAAACATTGTCATGGAGATGTTTGTATACTGAATGCCACAGAGTGGGTTAGAGAACACGCCT CTGGCTATGTCAGCAGAGATACTTCATCTTCACCCACCACAGGAAGCACAGTCCAGTCAGTTGA CCTCATCTTCACGAGACTCTGGATCTACAGCCATCATATCTATAACAAATGCAAAAGAAAGAAT ATTCTAGAGTGGGCAAAGGAGCTTTCCCTGTCTGGGTTTAGCATGCCTGGAAAACCTGGTGTTG TTTGTGTGGAAGGCCCACAAAGTGCCTGTGAAGAATTCTGGTCAAGACTCAGAAAATTAAACTG GAAGAGAATTTTAATTCGCCATCGAGAAGACATTCCTTTTGATGGTACAAATGATGAAACGGAA AGACAAAGGAAATTTTCCATTTTTGAAGAAAAAGTGTTCAGTGTTAATGGAGCCAGGGGAAACC ACATGGACTTTGGTCAGCTCTATCAGTTCTTAAACACCAAAGGATGTGGGGATGTTTTCCAGAT GTTCTTTGGTGTAGAAGGACAATGA CATCAAGAGTAGTTGAAAGTATCTTGCCACTGTTGGCCT TTTGATTTTTTTTTCCCACTTTTTCTTGAAACATTAAGTAATTTTATTTTAGTTCCATTCTAGA ATGTTGGGGAGTGGGGCACAAGAAAAAATAGTATAGCTGAAATGCATCTGTTAAAAATGTCATG ATTGAAAGCAGAACTGAGTTTCAAATTACAACCTTAAAATTGTTGTTAGATATTTCTTCACATA TCAGCTGCCCATTTTGAAAAAGAAATTATCCATAAAGGTAATGTTGGTGCTCCAATTTGCCAGC CATTCCCAACCCCCTTCTCCCTTACCTGCCTTCACTAAAGAACCCAGAAAAGCTAATTGCTCCC CTTTCAGCCTCTGTTGCAACTAACAACTCTCAGTGGCCTCAGGACACAGCTTTGGCCTTGGGAA TTCTCGGAAAACTTTTACTTCCTGATTAAAGATACATATGCAGCTAGGCCACCTCCTCCCCCCC TTACTGCCATAAACACCAAAGTGATGACTGGAGCTGGAGGAGTTATTTGAACCACGACGGAAGG GCCAAGAGAACCACGAAGATGCCAGTTGCCACATTGTTGAGCTGCTGACCCAACACCAGCCATT GCCTGTCTCTAAACATCTTATGAAATAAAACCAATTTTGTTTAAAAAAAAAAAAAAA ORF Start: ATG at 394                      ORF Stop: TGA at 1111 SEQ ID NO: 58               239 aa         MW at 27409.3 kD NOV14a, MLRLKTLVSALFLLLFNQAMFSLACILPFKYPAVLPEITVRSVLLSRSQQTQLNTDLTAFLQKH CG173318-01 Protein Sequence CHGDVCILNATEWVREHASGYVSRDTSSSPTTGSTVQSVDLIFTRLWIYSHHIYNKCKRKNILE WAKELSLSGFSMPGKPGVVCVEGPQSACEEFWSRLRKLNWKRILIRHREDIPFDGTNDETERQR KFSIFEEKVFSVNGARGNHMDFGQLYQFLNTKGCGDVFQMFFGVEGQ

[0420] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B. TABLE 14B Protein Sequence Properties NOV14a SignalP Cleavage site between residues 23 and 24 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 5; pos. chg 2; neg. chg 0 H-region: length 24; peak value 10.88 PSG score: 6.47 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −2.51 possible cleavage site: between 24 and 25 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood = −4.78 Transmembrane 11-27 PERIPHERAL Likelihood =   5.41 (at 133) ALOM score: −4.78 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 18 Charge difference: −2.0 C(1.0)-N(3.0) N >= C: N-terminal side will be inside >>> membrane topology: type 2 (cytoplasmic tail 1 to 11) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 4.83 Hyd Moment(95): 3.70 G content: 0 D/E content: 1 S/T content: 3 Score: −3.64 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 57 SRS|QQ NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.7% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: LRLK none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 34.8%: mitochondrial 30.4%: cytoplasmic 13.0%: Golgi  8.7%: endoplasmic reticulum  4.3%: vacuolar  4.3%: extracellular, including cell wall  4.3%: vesicles of secretory system >> indication for CG173318-01 is mit (k = 23)

[0421] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14C. TABLE 14C Geneseq Results for NOV14a Identities/ Similarities for Geneseq Protein/Organism/Length NOV14a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value AAE15253 Human RNA metabolism protein-16 19 . . . 239  221/221 (100%) e−131 (RMEP-16) - Homo sapiens, 319 aa. 99 . . . 319  221/221 (100%) [WO200183524-A2, 08 NOV. 2001] AAM78405 Human protein SEQ ID NO 1067 - 19 . . . 239  221/221 (100%) e−131 Homo sapiens, 319 aa. 99 . . . 319  221/221 (100%) [WO200157190-A2, 09 AUG. 2001] AAM79389 Human protein SEQ ID NO 3035 - 19 . . . 236 215/218 (98%) e−127 Homo sapiens, 354 aa. 137 . . . 354  216/218 (98%) [WO200157190-A2, 09 AUG. 2001] ABB11888 Human novel protein, SEQ ID 19 . . . 236 215/218 (98%) e−127 NO: 2258 - Homo sapiens, 354 aa. 137 . . . 354  216/218 (98%) [WO200157188-A2, 09 AUG. 2001] AAB58229 Lung cancer associated polypeptide 19 . . . 167 147/149 (98%) 9e−84  sequence SEQ ID 567 - Homo 103 . . . 251  147/149 (98%) sapiens, 305 aa. [WO200055180-A2, 21 SEP. 2000]

[0422] In a BLAST search of public sequence databases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D. TABLE 14D Public BLASTP Results for NOV14a Identities/ Protein Similarities for Accession NOV14a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value P57060 Protein C21orf6 (GL011) - Homo 19 . . . 239  221/221 (100%) e−130 sapiens (Human), 319 aa. 99 . . . 319  221/221 (100%) Q9DCJ3 Open reading frame 5 - Mus 21 . . . 239 182/219 (83%) e−105 musculus (Mouse), 244 aa. 26 . . . 244 192/219 (87%) Q99M03 Similar to open reading frame 5 - 21 . . . 239 182/219 (83%) e−105 Mus musculus (Mouse), 290 aa. 72 . . . 290 192/219 (87%) Q9JLH4 Orf5 protein - Mus musculus 21 . . . 239 181/219 (82%) e−105 (Mouse), 291 aa. 73 . . . 291 192/219 (87%) Q9D9S3 1700030C20Rik protein - Mus 23 . . . 239  85/222 (38%) 4e−38  musculus (Mouse), 292 aa. 72 . . . 288 127/222 (56%)

Example 15

[0423] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A. TABLE 15A NOV15 Sequence Analysis SEQ ID NO: 59          1776 bp NOV15a, CACCCGATCCACC ATGTCCGCGCTGCGACCTCTCCTGCTTCTGCTGCTGCCTCTGTGTCCCGGT CG50970-06 DNA Sequence CCTGGTCCCGGACCCGGGAGCGAGGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGC TGGGGGCCCGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCG GGTCTGTCCCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACT GAGGCCACCTTCCGAGGCCTGGTGGAGGACAGCGGCTCCTTTCTGGTTCACACACTGGCTGCCA GGCACAGAAAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCA GCTCTTCTCCCACTCCTACGGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTC TCTCGGCTGCGAGACTTCTATGGGGAATCTGGTGAGGGGTTGGATGACACCCTGGCGGATTTCT GGGCACAGCTCCTGGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTA CCTGCTCTGCCTCTCACGCTTGGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGGGGACTCA CCCCCGCCGCCTCCGCCTGCAGATAACCCGGACCCTGTGGCTGCCCGAGCCTTTGTGCAGGGCC TGGAGACTGGAAGAAATGTGGTCAGCGAAGCGCTTAAGGTGCCGGTGTCTGAAGGCTGCAGCCA GGCTCTGATGCGTCTCATCGGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAG GGCTTCTGCCTCAACGTGGTTCGTGGCTGTCTCAGCAGCAGGGGACTGGAGCCTGACTGGGGCA ACTATCTCGATGGTCTCCTGATCCTGGCTGATAAGCTCCAGGGCCCCTTTTCCTTTGAGCTGAC GGCCGAGTCCATTGGGGTGAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAG GTGTCCGCCCAGGTGTTTCAGGAGTGCGGCCCCCCCCGACCCGGTCCCTGCCCGAACCGTCGAG CCCCGCCGCCCCGGGAAGAGGCGGGCCGGCTGTGGTCGATGGTGACCGAGGAGGAGCGGCCCAC GACGGCCGCAGGCACCAACCTGCACCGGCTGGTGTGGGAGCTCCGCGAGCGTCTGGCCCGGATG CGGGGCTTCTGGGCCCGGCTGTCCCTGACGGTGTGCGGAGACTCTCGCATGGCAGCGGACGCCT CGCTGGAGGCGGCGCCCTGCTGGACCGGAGCCGGGCGGGGCCGGTACTTGCCGCCAGTGGTCGG GGGCTCCCCGGCCGAGCAGGTCAACAACCCCGAGCTCAAGGTGGACGCCTCGGGCCCCGATGTC CCGACACGGCGGCGTCGACTACAGCTCCGGGCGGCCACGGCCAGAATGAAAACGGCCGCACTGG GACACGACCTGGACGGGCAGGACGCGGATGAGGATGCCAGCGGCTCTGGAGGGGGACAGCAGTA TGCAGATGACTGGATGGCTGGGGCTGTCGCTCCCCCAGCCCCGCCTCCTCGGCCTCCATACCCT CCTAGAAGGGATGGTTCTGGGGGCAAAGGAGGAGGTGGCAGTGCCCGCTACAACCAGGGCCGGA GCAGGAGTGGGGGGGCATCTATTGGTTTTCACACCCAAACCATCCTCATTCTCTCCCTCTCAGC CCTGGCCCTGCTTGGACCTCGACTC GAGGGCGGGCGAATTCCAGCA ORF Start: ATG at 14                   ORF Stop: at 1751 SEQ ID NO: 60           579 aa         MW at 62828.7 kD NOV15a, MSALRPLLLLLLPLCPGPGPGPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQ CG50970-06 Protein Sequence EYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSH SYGRLYAQHALIFNGLFSRLRDFYGESGEGLDDTLADFWAQLLERVFPLLHPQYSFPPDYLLCL SRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMR LIGCPLCRGVPSLMPCQGFCLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESI GVKISEGLMYLQENSAKVSAQVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAG TNLHRLVWELRERLARMRGPWARLSLTVCGDSRMAADASLEAAPCWTGAGRGRYLPPVVGGSPA EQVNNPELKVDASGPDVPTRRRRLQLRAATARMKTAALGHDLDGQDADEDASGSGGGQQYADDW MAGAVAPPARPPRPPYPPRRDGSGGKGGGGSARYNQGRSRSGGASIGFHTQTILILSLSALALL GPR SEQ ID NO: 61          1785 bp NOV15b, ATGTCCGCGCTGCGACCTCTCCTGCTTCTGCTGCTGCCTCTGTGTCCCGGTCCTGGTCCCGGAC CG50970-01 DNA Sequence CCGGGAGCGAGGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGCTGGGGGCCCGGGG ATATAGCTTAAACCTAACCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGGGTCTGTCCCCCAG GAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACTGAGGCCACCTTCC GAGGCCTGGTGGAGGACAGCGGCTCCTTTCTGGTTCACACACTGGCTGCCAGGCACAGAAAAAT TGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCAGCTCTTCTCCCAC TCCTACGGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCGGCTGCGAG ACTTCTATGGGGAATCTGGTGAGGGGTTGGATGACACCCTGGCGGATTTCTGGGCACAGCTCCT GGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGCTCTGCCTC TCACGCTTGGCCTCATCTACCGATGGCTCTCTGCCGCCCTTTGGGGACTCACCCCGCCGCCTCC GCCTGCAGATAACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCCTGGAGACTGGAAG AAATGTGGTCAGCGAAGCGCTTAAGGTTCCGGTGTCTGAAGGCTGCAGCCAGGCTCTGATGCGT CTCATCGGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGGGCTTCTGCCTCA ACGTGGTTCGTGGCTGTCTCAGCAGCAGGGGACTGGAGCCTGACTGGGGCAACTATCTGGATGG TCTCCTGATCCTGGCTGATAAGCTCCAGGGCCCCTTTTCCTTTGAGCTGACGGCCGAGTCCATT GGGGTGAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAGGTGTCCGCCCAGG TATTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGAACCGTCGAGCCCCGCCGCCCCCG GGAAGAGGCGGGCCGGCTGTGGTCGATGGTGACCGAGGAGGAGCGGCCAACGACCGCCGCAGGC ACCAACCTGCACCGGCTGGTGTGGGAGCTCCGCGAGCGTCTGGCCCGGATGCGGGGCTTCTGGG CCCGGCTGTCCCTGACGGTGTGCGGAGACTCTCGCATGGCAGCGGACGCCTCGCTGGAGGCGGC GCCCTGCTGGACCGGAGCCGGGCGGGGCCGGTACTTGCCGCCAGTGGTCGGGGGCTCCCCGGCC GAGCAGGTCAACAACCCCGAGCTCAAGGTGGACGCCTCGGGCCCCGATGTCCCGACACGGCGGC GTCGGCTACAGCTCCGGGCGGCCACGGCCAGAATGAAAACGGCCGCACTGGGACACGACCTGGA CGGGCAGGACGCAGATGAGGATGCCAGCGGCTCTGGAGGGGGACAGCAGTATGCAGATGACTGG ATGGCTGGGGCTGTGGCTCCCCCAGCCCGGCCTCCTCGGCCTCCATACCCTCCTAGAAGGGATG GTTCTGGGGGCAAAGGAGGAGGTGGCAGTGCCCGCTACAACCAGGGCCGGAGCAGGAGTGGGGG GGCATCTATTGGTTTTCACACCCAAACCACCTCATTCTCTCCCTCTCAGCCCCTGGCCCTGCTT GGACCTCGATAA CGGGGGAGGGGTGCCCTAGCATCAGAAGGGTTCATGGCCCTTTCC ORF Start: ATG at 1                    ORF Stop: TAA at 1738 SEQ ID NO: 62           579 aa         MW at 62828.7 kD NOV15b, MSALRPLLLLLLPLCPGPGPGPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQ CG50970-01 Protein Sequence EYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSH SYGRLYAQHALIFNCLFSRLRDFYGESGEGLDDTLADPWAQLLERVFPLLHPQYSFPPDYLLCL SRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMR LIGCPLCRGVPSLMPCQGFCLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESI GVKISEGLMYLQENSAKVSAQVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAG TNLHRLVWELRERLARMRGFWARLSLTVCGDSRMAADASLEAAPCWTGAGRGRYLPPVVGGSPA EQVNNPELKVDASGPDVPTRRRRLQLRAATARMKTAALGHDLDGQDADEDASGSGGGQQYADDW MAGAVAPPARPPRPPYPPRRDGSGGKGGGGSARYNQGRSRSGGASIGFHTQTILILSLSALALL GPR SEQ ID NO: 63          1648 bp NOV15d, C ACCGGATCCAGCGAGGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGCTGGGGGCC 274054257 DNA Sequence CGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGGGTCTGTC CCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACTGAGGCCAC CTTCCGAGGCCTGGTGGAGGACAGCGGCTCCTTTCTGGTTCACACACTGGCTGCCAGGCACAGA AAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCAGCTCTTCT CCCACTCCTACGGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCGGCT GCGAGACTTCTATGGGGAATCTGGTGAGGGGTTGGATGACACCCTGGCGGATTTCTGGGCACAG CTCCTGGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGCTCT GCCTCTCACGCTTGGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGGGGACTCACCCCGCCG CCTCCGCCTGCAGATAACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCCTGGAGACT GGAAGAAATGTGGTCAGCGAAGCGCTTAAGGTGCCGGTGTCTGAAGGCTGCAGCCAGGCTCTGA TGCGTCTCATCGGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGGGCTTCTG CCTCAACGTGGTTCGTGGCTGTCTCAGCAGCAGGGGACTGGAGCCTQACTGGGGCAACTATCTG GATGGTCTCCTGATCCTGGCTGATAAGCTCCAGGGCCCCTTTTCCTTTGAGCTGACGGCCGAGT CCATTGGGGTGAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAGGTGTCCGC CCAGGTGTTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAGCCCCGCCG CCCCGGGAAGAGGCGGGCCGGCTGTGGTCGATGGTGACCGAGGAGGAGCGGCCCACGACGGCCG CAGGCACCAACCTGCACCGGCTGGTGTGGGAGCTCCGCGAGCGTCTGGCCCGGATGCGGGGCTT CTGGGCCCGGCTGTCCCTGACGGTGTGCGGAGACTCTCGCATGGCAGCGGACGCCTCGCTGGAG GCGGCGCCCTGCTGGACCGGAGCCGGGCGGGGCCGGTACTTGCCGCCAGTGGTCGGGGGCTCCC CGGCCGAGCAGGTCAACAACCCCGAGCTCAAGGTGGACGCCTCGGGCCCCGATGTCCCGACACG GCGGCGTCGGCTACAGCTCCGGGCGGCCACGGCCAGAATGAAAACGGCCGCACTGGGACACGAC CTGGACGGGCAGGACGCGGATGAGGATGCCAGCGGCTCTGGAGGGQGACAGCAGTATGCAGATG ACTGGATGGCTGGGGCTGTGGCTCCCCCAGCCCGGCCTCCTCGGCCTCCATACCCTCCTAGAAG GGATGGTTCTGGGGGCAAAGGAGGAGGTGGCAGTGCCCGCTACAACCAGGGCCGGAGCAGGAGT GCGCGGGCATCTATTCGTTTTCACACCCAAACCATCCTCCTCGAGGGC ORF Start: at 2                        ORF Stop: end of sequence SEQ ID NO: 64           549 aa         MW at 59802.9 kD NOV15d, TGSSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQEYTCCSSETEQRLIRETEAT 274054257 Protein Sequence FRGLVEDSGSFLVUTLAARHRKFDEFFLEMLSVAQHSLTQLFSHSYGRLYAQHALIFNGLFSRL RDFYGESGEGLDDTLADFWAQLLERVFPLLHPQYSFPPDYLLCLSRLASSTDGSLQPFGDSPRR LRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMRLIGCPLCRGVPSLMPCQGFC LNVVRQCLSSRGLEPDWGNYLDGLLTLADKLQGPFSFELTAESIGVKISEGLMYLQENSAKVSA QVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAGTNLHRLVWELRERLARMRGF WARLSLTVCGDSRMAADASLEAAPCWTGAGRGRYLPPVVGGSPAEQVNNPELKVDASGPDVPTR RRRLQLRAATARMKTAALGHDLDGQDADEDASGSGGCQQYADDWMAGAVAPPARPPRPPYPPRR DGSGGKGGGGSARYNQGRSRSGGASIGFHTQTILLEG SEQ ID NO: 65          1613 bp NOV15e, ATGTCCGCCCTGCCACCTCTCCTGCTTCTGCTGCTGCCTCTGGGTCCCGGTCCTGGTCCCGGAC CG50970-03 DNA Sequence CCGGGAGCGAGGCAAAGGTCACCCGGAGTTGTCCAGAGACCCGGCACGTGCTGGCGGCCCGGGG ATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGGGTCTGTCCCCAG GAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACTGAGGCCACCTTCC GAGGCCTCGTGGAGGACAGCGGCTCCTTTCTCGTTCACACACTGGCTGCCAGGCACACAAAATT TGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCAGCTCTTCTCCCAC TCCTACCGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCCGCTGCGAG ACTTCTATGGGGAATCTCGTGAGGGGTTGGATGACACCCTGGCGGATTTCTGGGCACAGCTCCT GGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGCTCTGCCTC TCACGCTTGGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGGGGACTCACCCCGCCGCCTCC GCCTGCAGATAACCCGGACCCTGGTCGCTGCCCGAGCCTTTGTGCAGGGCCTGGAGACTGGAAG AAATGTGGTCAGCGAAGCGCTTAAGGTGCCGGTGTCTGAAGGCTGCAGCCAGGCTCTGATGCGT CTCATCCGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGGGCTTCTGCCTCA ACGTGGTTCGTGGCTGTCTCAGCAGCAGGGGACTGGAGCCTGACTGGGGCAACTATCTGGATGG TCTCCTGATCCTGGCTGATAAGCTCCAGGGCCCCTTTTCCTTTGAGCTGACGGCCGAGTCCATT GCGGTGAAGATCTCCGACGGTTTGATGTACCTGCAGGAAAACAGTGCGAAGGTGTCCGCCCAGG TGTTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAGCCCCGCCGCCCCG GGAACAGGCGGGCCGGCTGTGGTCGATGGTCACCGACGAGGAGCGGCCCACGACGGCCGCAGGC ACCAACCTGCACCGGCTGGTACTTGCCGCCAGTGGTCGGGGGCTCCCCGGCCGAGCAGGTCAAC AACCCCGAGCTCAAGGTGGACGCCTCGGGCCCCGATGTCCCGACACCGCGGCGTCCGCTACAGC TCCGGGCCGCCACGGCCAGAATGAAAACGGCCGCACTGCGACACGACCTGGACGCGCAGGACGC GGATGA GGATGCCAGCGGCTCTGGAGGGGGACAGCAGTATGCAGATGACTGGATGGCTGGGGCT GTCGCTCCCCCACCCCGGCCTCCTCCGCCTCCATACCCTCCTAGAACGGATGGTTCTGGGGGCA AAGGAGGAGGTGGCAGTGCCCGCTACAACCAGGGCCCGAGCAGGAGTGGGGGCGCATCTATTCG TTTTCACACCCAAACCATCCTCATTCTCTCCCTCTCAGACCTGGCCCTGCTTGGACCTCGATAA CCGGGGAGGGGTG ORF Start: ATG at 1                    ORF Stop: TGA at 1348 SEQ ID NO: 66          1449 aa         MW at 48717.0 kD NOV15e MSALRPLLLLLLPLCPGPGPGPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQ CG50970-03 Protein Sequence EYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSH SYGRLYAQHALIFNGLFSRLRDFYGESGEGLDDTLADFWAOLLERVFPLLHPQYSFPPDYLLCL SRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMR LIGCPLCRGVPSLMPCQGFCLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESI GVKISEGLMYLQELSAKVSAQVFQECGPPDPVPARNRRAPPPREEAQRLWSMVTEEERPTTAAG TNLHRLVLAASGRGLPGRAGQQPRAQGGRLGPRCPDTAASATAPGGHGQNENGRTGTRPGRAGR G SEQ ID NO: 67          1297 bp NOV15f, C ACCGGATCCACCAGCGAGGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCACGTCCTGGCG 237922026 DNA Sequence GCCCGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGGGTCT GTCCCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCACGGAGACTGAGCC CACCTTCCGAGGCCTGGTGGAGGACAGCGGCTCCTTTCTGGTTCACACACTGGCTGCCAGGCAC AGAAAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAQCACTCTCTGACCCAGCTCT TCTCCCACTCCTACCGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCG GCTCCGAGACTTCTATGCGGAATCTGGTGAGGGGTTGGATCACACCCTGGCGOATTTCTGGGCA CAGCTCCTGGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGC TCTGCCTCTCACGCTTGGCCTCATCTACCGATGQCTCTCTGCAGCCCTTTGCGGACTCACCCCG CCGCCTCCGCCTGCAGATAACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCCTGGAG ACTGGAAGAAATGTGGTCAGCCAAGCGCTTAAGGTCCCCGTGTCTGAAGGCTGCAGCCAGGCTC TGATGCGTCTCATCGGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGGGCTT CTGCCTCAACGTGGTTCGTCGCTGTCTCAGCAGCAGGGGACTGGAGCCTGACTCCGGCAACTAT CTGGATGGTCTCCTGATCCTCGCTGATAAGCTCCACGGCCCCTTTTCCTTTGAGCTGACGGCCG AGTCCATTGGGGTGAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAGGTGTC CGCCCAGGTGTTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAGCCCCG CCGCCCCGGGAAGAGGCGGGCCGGCTGTGGTCGATCGTGACCGAGGACGAGCGGCCCACGACGG CCGCAGGCACCAACCTGCACCGGCTGGTACTTGCCGCCAGTGGTCGGGGGCTCCCCGGCCGAGC AGGTCAACAACCCCGAGCTCAAGGTGGACGCCTCGGGCCCCGATCTCCCGACACGGCGGCGTCG GCTACAGCTCCGGGCCGCCACGGCCAGAATGAAAACGGCCGCACTCGGACACGACCTGGACGGG CAGGACGCGGACTCGAG ORF Start: at 2                        ORF Stop: end of sequence SEQ ID NO: 68           432 aa         MW at 47040.8 kD NOV15f, TCSTSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQEYTCCSSETEQRLIRETEA 237922026 Protein Sequence TFRGLVEDSGSFLVHTLAARHRKFDEPPLEMLSVAQHSLTQLFSHSYGRLYAQHALIFNGLFSR LRDFYGESGEGLDDThADFWAQLLERVFPLLHPQYSFPPDYLLCLSRLASSTDGSLQPFGDSPR RLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMRLIGCPLCRGVPSLMPCQGP CLNVVRGCLSSRGLEPDWCNYLDGLLTLADKLQGPPSFELTAESIQVKISEGLMYLQENSAKVS AQVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAGTNLHRLVLAASGRGLPGRA GQQPRAQCGRLGPRCPDTAASATAPGGHCQNENGRTGTRPCRAGRGLE SEQ ID NO: 69          1126 bp NOV15g, C ACCGGATCCACCAGCGAGGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGCTCGGG 237922511 DNA Sequence GCCCGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGGGTCT GTCCCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGCGAGACTGAGGC CACCTTCCGAGGCCTGGTGGAGGACAGCGGCTCCTTTCTCGTTCACACACTGGCTGCCAGGCAC AGAAAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCAGCTCT TCTCCCACTCCTACGGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCG GCTGCGAGACTTCTATGGGGAATCTGGTGAGGGGTTGGATGACACCCTGGCGGATTTCTGGGCA CAGCTCCTGGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGC TCTGCCTCTCACGCTTGGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGCGGACTCACCCCG CCGCCTCCGCCTGCAGATAACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCCTGGAG ACTCGAAGAAATGTGGTCAGCGAAGCGCTTAAGGTGCCGGTGTCTGAAGGCTGCAGCCAGGCTC TGATGCGTCTCATCCGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGCGCTT CTGCCTCAACGTGGTTCGTGGCTGTCTCAGCAGCAGGGGACTGGAGCCTGACTGGGGCAACTAT CTGGATGGTCTCCTGATCCTCGCTCATAAGCTCCAGGGCCCCTTTTCCTTTGAGCTGACGGCCG AGTCCATTGGGGTGAAGATCTCGGACGGTTTGATGTACCTGCAGGAAAACAGTCCGAAGGTGTC CGCCCAGGTGTTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAGCCCCG CCGCCCCGGGAAGAGGCCGGCCCGCTGTGGTCGATGGTGACCGAGGAGGAGCGGCCCACGACGG CCGCAGGCACCAACCTGCACCGGCTGGTACTTCTCGAG ORF Start: at 2                        ORF Stop: end of sequence SEQ ID NO: 70           375 aa         MW at 41526.8 kD NOV15g, TGSTSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQEYTCCSSETEQRLIRETEA 237922511 Protein Sequence TFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSHSYCRLYAQHALIFNGLFSR LRDFYGESGEGLDDTLADFWAQLLERVPPLLHPQYSFPPDYLLCLSRLASSTDGSLQPFGDSPR RLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMRLIGCPLCRGVPSLMPCQGF CLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESIGVKISEGLMYLQENSAKVS AQVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAGTNLHRLVLLE SEQ ID NO: 71          1776 bp NOV15h, C ACCGGATCCACCATGTCCGCGCTGCGACCTCTCCTGCTTCTGCTGCTGCCTCTGTGTCCCGGT 315490136 DNA Sequence CCTGGTCCCGGACCCCGGAGCGAGGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGC TGGCGGCCCGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCG GGTCTGTCCCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACT GAGGCCACCTTCCGAGGCCTGGTGGAGGACAGCGGCTCCTTTCTGGTTCACACACTGGCTGCCA GGCACAGAAAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCA GCTCTTCTCCCACTCCTACGGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTC TCTCGGCTGCGAGACTTCTATGCGGAATCTGGTCAGGGGTTGGATGACACCCTCGCGGATTTCT GGGCACAGCTCCTGGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTA CCTGCTCTGCCTCTCACGCTTGGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGGGGACTCA CCCCGCCGCCTCCGCCTGCAGATAACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCC TGGAGACTGGAAGAAATGTGGTCAGCGAAGCGCTTAAQGTGCCGGTGTCTGAAGGCTGCAGCCA CGCTCTGATCCGTCTCATCGGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAG GGCTTCTGCCTCAACGTGGTTCGTGGCTGTCTCAGCAGCAGCGGACTGGAGCCTGACTGGGGCA ACTATCTGGATCGTCTCCTGATCCTCGCTGATAAGCTCCAGGGCCCCTTTTCCTTTGACCTGAC GGCCGAGTCCATTGGGGTGAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAG GTGTCCGCCCAGGTGTTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAG CCCCGCCGCCCCGGGAAGACGCGGGCCGGCTGTCGTCGATGGTGACCGAGGAGGAGCGGCCCAC GACGGCCGCAGGCACCAACCTGCACCGGCTGGTGTGGGAGCTCCGCGAGCGTCTGGCCCCGATG CGGGGCTTCTGCGCCCGGCTGTCCCTGACGGTGTGCGGAGACTCTCGCATGGCAGCGGACGCCT CGCTGGAGGCGGCGCCCTGCTGGACCGGACCCGGGCGGGGCCGGTACTTGCCGCCAGTGGTCGG GGGCTCCCCGGCCGAGCAGGTCAACAACCCCGAGCTCAAGGTGGACGCCTCGGGCCCCGATGTC CCGACACGGCGGCGTCGACTACAGCTCCGGGCGGCCACGGCCAGAATGAAAACGGCCGCACTGG GACACGACCTGGACGGGCAGGACGCCGATGAGGATGCCAGCGGCTCTCGAGGGGGACAGCAGTA TGCAGATGACTGGATGGCTGGGGCTGTCGCTCCCCCAGCCCGGCCTCCTCGGCCTCCATACCCT CCTAGAAGGGATGGTTCTGGGGGCAAACGAGGACGTGGCAGTGCCCGCTACAACCAGGGCCGGA GCACGAGTGGGCGGGCATCTATTCGTTTTCACACCCAAACCATCCTCATTCTCTCCCTCTCAGC CCTGGCCCTGCTTGGACCTCGACTCGAGGGCAAGGGCGAATTCCAGCA ORF Start: at 2                        ORF Stop: end of sequence SEQ ID NO: 72           592 aa         MW at 64064.0 kD NOV15h, TGSTMSALRPLLLLLLPLCPGPGPGPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLR 315490136 Protein Sequence VCPQEYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQ LFSHSYGRLYAQHALIFNGLFSRLRDFYGESGEGLDDTLADFWAQLLERVFPLLHPQYSFPPDY LLCLSRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQQLETGRNVVSEALKVPVSEGCSQ ALMRLIGCPLCRGVPSLMPCQGFCLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELT AESIGVKISEGLMYLQENSAKVSAQVFQECGPPDPVPAPNRRAPPPRESAGRLWSMVTEEERPT TAAGTNLHRLVWELRERLARMRGFWARLSLTVCGDSRMAADASLEAAPCWTGAGRGRYLPPVVG GSPAEQVNNPELKVDASGPDVPTRRRRLQLRAATARMKTAALGHDLDGQDADEDASGSGGGQQY ADDWMAGAVAPPARPPRPPYPPRRDGSGGKGGGGSARYNQQRSRSGGASIGFHTQTILILSLSA LALLCPRLEGKGEFQX SEQ ID NO: 73          1976 bp NOV15i, GGCTCTGCTTTCCTCCTTAGGACCCACTTTGCCGTCCTGGGGTGGCTGCAGTT ATGTCCGCGCT CG50970-02 DNA Sequence GCGACCTCTCCTGCTTCTGCTGCTGCCTCTGTGTCCCGGTCCTGGTCCCCGACCCGGGAGCGAG GCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGCTGGGGGCCCCGGGATATAGCTTAA ACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGGGTCTGTCCCCAGGAGTACACCTG CTGTTCCACTGAGACAGAGCAGACGCTGATCAGGGAGACTGAGGCCACCTTCCGAGGCCTGGTG GAGGACAGCQGCTCCTTTCTGGTTCACACACTGGCTGCCAGGCACAGAAAATTTGATGAGTTTT TTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCAGCTCTTCTCCCACTCCTACGGCCG CCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCGGCTGCGAGACTTCTATGCG GAATCTGGTGACGGGTTGGATGACACCCTGGCGGATTTCTGCGCACAGCTCCTGCAGAGAGTGT TCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGCTCTGCCTCTCACGCTTGGC CTCATCTACCGATGGCTCTCTGCAGCCCTTTCGCGACTCACCCCGCCGCCTCCGCCTGCAGATA ACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCCTGGAGACTGGAAGAAATGTCGTCA GCGAAGCGCTTAAGGTTCCGGTGTCTGAAGGCTGCAGCCAGGCTCTGATGCGTCTCATCGGCTG TCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGGGCTTCTGCCTCAACGTGGTTCGT GGCTGTCTCAGCAGCAGGGGACTGGAGCCTGACTGGGGCAACTATCTGGATGGTCTCCTGATCC TGGCTGATAACCTCCAGCGCCCCTTTTCCTTTGAGCTGACGGCCGAGTCCATTGGGGTGAAGAT CTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAGGTGTCCGCCCAGGTATTTCAGGAG TGCGCCCCCCCCGACCCCGTGCCTGCCCGCAACCGTCGAGCCCCGCCGCCCCCGGAAGACGCCG GCCGGCTGTGGTCGATGGTGACCGAGGAGGAGCGGCCAAGCGCACATGACGATGCCAGCGGCTC TGGAGGGGGACAGCAGTATGCAGATGACTGGATGGCTGGGGCTGTGGCTCCCCCAGCCCGGCCT CCTCCGCCTCCATACCCTCCTAGAAGGGATGGTTCTGGGGGCAAAGGAGGAGGTGGCAGTGCCC GCTACAACCAGGGCCGGAGCAGGAGTGCGGGGGCATCTATTGGTTTTCACACCCAAACCATCCT CATTCTCTCCCTCTCAGCCCTGGCCCTGCTTCGACCTCGATAA CCGGGGACGGGTGCCCTAGCA TCAGAAGGGTTCATGGCCCTTTCCCCTCCTCCCCCCTCAGCTGGGCCTGGGGAGGAGTCGAAGG GCGCTGCAGAGACGGTAGAGAAGGGACTTTGCACGTGAATGGCTGGGGCCCCAAATCCAGGAGA TTTTCATCAGAGGTGGGTGGGTGTTCACAATATTTATTTTTTCATTTGGTAATGGGAGGGGGGC CTGGGGGTATTTATTTAGGAGGGAGTGTGGTTTCCTTAGAAGGTATAGTCTCTAGCCCTCTAAG GCTCGGCCTGGTGATCAGCCCCAACAGAGAAAATGACGAGTTTAGAGTTGCAGCTGGGTTCTGT TGAGTTTTTTCAGTATCAATTTCTTAAACCAAATTTTAAAAAAAACAAGGTCGGCGGGTGCTCA TCTCGTGACCTCTGCCACCCACATCCTTCACAAACTCCATGTTTCAGTGTTTGAGTCCATGTTT ATTCTGCAATAAATCGTAATGTATTAAAAAAAAAAAAAAAAAAAAAAAAAAAA ORF Start: ATG at 54                   ORF Stop: TAA at 1449 SEQ ID NO: 74           465 aa         MW at 50470.8 kD NOV15i, MSALRPLLLLLLPLCPGPGPGPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQ CG50970-02 Protein Sequence EYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSH SYGRLYAQHALIFNGLFSRLRDFYCESGECLDDTLADFWAQLLERVFPLLHPQYSFPPDYLLCL SRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMR LIGCPLCRGVPSLMPCQGPCLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESI GVKISEGLMYLQENSAKVSAQVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPSADED ASGSGGGQQYADDWMAGAVAPPARPPRPPYPPRRDGSGGKGGCGSARYNQGRSRSGGASIGFHT QTILILSLSALALLGPR SEQ ID NO: 75           725 bp NOV15j, CGCCTGGTCCAGCTATCGTGCTCCGTATTCAGTTTTCCCGAGCAGCGCTCTTTCTCTGGCCCGC CG50970-04 DNA Sequence GGAACGGTCCCGCQGCCGAGTACCGGATTCCCGAGTTTGGGAGGCTCTGCTTTCCTCCTTAGGA CCCACTTTGCCGTCCTGGGGTGGCTGCAGTT ATGTCCGCGCTGCGACCTCTCCTGCTTCTGCTG CTGCCTCTGTGTCCCGGTCCTGGTCCCGGACCCGGGAGCGAGGCAAAGGTCACCCGGAGTTGTG CAGAGACCCGGCAGGTGCTGGGGGCCCGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGAT CTCAGGTGAGCACCTCCGGGTCTGTCCCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAG AGGCTGATCAGGGAGACTGAGGCCACCTTCCGAGGCCTGGTGGAGGACAGCGGCTCCTTTCTGG TTCACACACTGGCTGCCAGGCACAGAAAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGC CCCGCCTCCTCGGCCTCCATACCCTCCTAGAAGCGATGGTTCTGGGGGCAAAGGAGGAGGTGGC AGTGCCCGCTACAACCAGGGCCGGAGCAGGAGTGGGGGGGCATCTATTGGTTTTCACACCCAAA CCATCCTCATTCTCTCCCTCTCAGCCCTGGCCTTGCTTGCACCTCGATAA CGGGCGAGGGGTGC CCTAGCATCAGAAGGGTTCAT ORF Start: ATG at 160                  ORF Stop: TAA at 688 SEQ ID NO: 76           176 aa         MW at 18879.4 kD NOV15j, MSALRPLLLLLLPLCPGPGPGPGSEMCVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQ CG50970-04 Protein Sequence EYTCCSSETEQRLTRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVARPPRPPYPPR RDGSGGKGGGGSARYNQGRSRSGGASIGFHTQTILILSLSALALLGPR SEQ ID NO: 77          1590 bp NOV15k, AGCGAGGCAAAGGTCACCCGGAGTTGTGCACAGACCCGGCAGGTGCTGGGGGCCCGGGGATATA CG50970-05 DNA Sequence GCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCGCGTCTGTCCCCAGGAGTA CACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACTGAGGCCACCTTCCGAGGC CTGGTGGAGGACAGCCGCTCCTTTCTGGTTCACACACTGGCTGCCAGGCACAGAAAATTTGATG AGTTTTTTCTGGAGATGCTCTCAGTAGCCCAACACTCTCTGACCCAGCTCTTCTCCCACTCCTA CCGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTCTCTCGGCTGCGAGACTTC TATGGGGAATCTGGTCACGCGTTGGATGACACCCTGGCGGATTTCTGGGCACAGCTCCTGGAGA GAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTACCTGCTCTGCCTCTCACG CTTCGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGGGGACTCACCCCGCCGCCTCCGCCTG CAGATAACCCGGACCCTGGTGGCTGCCCGAGCCTTTGTGCAGGGCCTGGAGACTGGAAGAAATG TGGTCAGCGAAGCGCTTAAGGTGCCGGTGTCTGAACGCTGCAGCCAGGCTCTGATGCGTCTCAT CGGCTGTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAGGGCTTCTGCCTCAACGTG GTTCGTGGCTGTCTCAGCACCAGGGGACTGGAGCCTGACTGGGGCAACTATCTGGATGGTCTCC TGATCCTGGCTGATAAGCTCCACGGCCCCTTTTCCTTTGAGCTGACGGCCGAGTCCATTGGGGT GAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAGGTGTCCGCCCAGGTGTTT CAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAGCCCCGCCGCCCCGGCAAG AGGCGGGCCGGCTGTCGTCGATGGTGACCGAGGAGGAGCCGCCCACGACGGCCGCAGGCACCAA CCTGCACCGGCTGGTGTGGGAGCTCCGCGAGCGTCTGGCCCGGATGCGGGGCTTCTGCGCCCGG CTGTCCCTGACGGTGTGCGGAGACTCTCGCATGGCAGCGGACGCCTCGCTGGAGGCAGCGCCCT GCTGGACCGGAGCCGGGCGGGGCCGGTACTTGCCGCCAGTGGTCGGGGGCTCCCCGGCCGAGCA GGTCAACAACCCCGAGCTCAACGTGGACGCCTCGGGCCCCGATGTCCCGACACGGCGGCGTCGG CTACCGCTCCGCGCGGCCACGGCCAGAATGAAAACGGCCGCACTGGGACACCACCTGGACGGGC AGGACGCGGATGAGGATGCCAGCGGCTCTGGAGGGCGACAGCAGTATGCAGATGACTGGATGGC TCGGGCTGTGGCTCCCCCAGCCCGGCCTCCTCGGCCTCCATACCCTCCTAGAAGGGATGGTTCT GGGGGCAAACGACGAGGTGGCAGTGCCCGCTACAACCAGGGCCGGAGCAGGAGT ORF Start: at 1                        ORF Stop: end of sequence SEQ ID NO: 78           530 aa         MW at 57988.9 kD NOV15k, SEAKVTRSCAETRQVLCARGYSLNLIPPALISGEHLRVCPQEYTCCSSETEQRLIRETEATFRG CG50970-05 Protein Sequence LVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSHSYGRLYAQHALIFNGLFSRLRDF YGESGEGLDDTLADFWAQLLERVFPLLHPQYSFPPDYLLCLSRLASSTDGSLQPFGDSPRRLRL QITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMRLIGCPLCRGVPSLMPCQGFCLNV VRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESIGVKISEGLMYLQENSAKVSAQVF QECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAGTNLHRLVWELRERLARMRGFWAR LSLTVCGDSRMAADASLEAAPCWTGAGRGRYLPPVVGGSPAEQVNNPELNVDASGPDVPTRRRR LRLRAATARMKTAALGHDLDGQDADEDASGSGGGQQYADDWMAGAVAPPARPPRPPYPPRRDGS GGKGCGQSARYNQGRSRS SEQ ID NO: 79          1762 bp NOV15l, CACCGGATCCACC ATGTCCGCGCTGCGACCTCTCCTGCTTCTGCTGCTGCCTCTGTGTCCCGGT CG50970-07 DNA Sequence CCTGGTCCCGGACCCGGGAGCGACGCAAAGGTCACCCGGAGTTGTGCAGAGACCCGGCAGGTGC TGGGGGCCCGGGGATATAGCTTAAACCTAATCCCTCCCGCCCTGATCTCAGGTGAGCACCTCCG GGTCTGTCCCCAGGAGTACACCTGCTGTTCCAGTGAGACAGAGCAGAGGCTGATCAGGGAGACT GAGGCCACCTTCCGAGGCCTGGTGGAGGACAGCCGCTCCTTTCTGGTTCACACACTGGCTGCCA GGCACAGAAAATTTGATGAGTTTTTTCTGGAGATGCTCTCAGTAGCCCAGCACTCTCTGACCCA GCTCTTCTCCCACTCCTACCGCCGCCTGTATGCCCAGCACGCCCTCATATTCAATGGCCTGTTC TCTCGGCTGCGAGACTTCTATGGGGAATCTCGTCACGGGTTCGATGACACCCTGGCGGATTTCT GCGCACAGCTCCTGGAGAGAGTGTTCCCGCTGCTGCACCCACAGTACAGCTTCCCCCCTGACTA CCTGCTCTGCCTCTCACGCTTGGCCTCATCTACCGATGGCTCTCTGCAGCCCTTTGGGGACTCA CCCCGCCGCCTCCGCCTGCAGATAACCCGGACCCTCGTGGCTGCCCGAGCCTTTGTGCAGGGCC TGGAGACTGGAAGAAATGTGGTCAGCGAAGCGCTTAAGGTGCCGGTGTCTGAAGGCTGCAGCCA GGCTCTGATGCGTCTCATCGGCTCTCCCCTGTGCCGGGGGGTCCCCTCACTTATGCCCTGCCAG GGCTTCTCCCTCAACGTGGTTCGTGGCTGTCTCAGCAGCAGGGGACTGGAQCCTGACTGGGGCA ACTATCTGGATGGTCTCCTGATCCTGGCTGATAAGCTCCAGGGCCCCTTTTCCTTTGAGCTGAC GGCCGAGTCCATTGGGGTGAAGATCTCGGAGGGTTTGATGTACCTGCAGGAAAACAGTGCGAAG GTGTCCGCCCACGTGTTTCAGGAGTGCGGCCCCCCCGACCCGGTGCCTGCCCGCAACCGTCGAG CCCCGCCGCCCCGGGAAGAGGCGGGCCGGCTGTCGTCGATGGTGACCGAGGAGGAGCCGCCCAC CACGGCCGCAGGCACCAACCTGCACCGGCTGGTGTGGGAGCTCCGCGAGCGTCTGGCCCGGATG CGGGGCTTCTGGGCCCGGCTGTCCCTGACGGTGTGCGGAGACTCTCGCATGGCAGCGGACGCCT CGCTGGAGGCGGCGCCCTGCTGGACCGGAGCCGGGCGGGGCCGGTACTTGCCGCCAGTGGTCGG GGGCTCCCCGGCCGAGCAGGTCAACAACCCCGAGCTCAAGGTGGACGCCTCCGGCCCCGATGTC CCGACACGGCGGCGTCGGCTACAGCTCCGGGCGGCCACGGCCAGAATGAAAACGGCCGCACTGG GACACGACCTGGACCGGCAGGACGCGGATGAGGATGCCAGCGGCTCTGGAGGGGGACAGCAGTA TGCAGATGACTGGATGGCTGGGGCTGTGGCTCCCCCAGCCCGGCCTCCTCGGCCTCCATACCCT CCTAGAAGGGATGGTTCTGGGGGCAAAGGAGGAGGTGGCAGTGCCCGCTACAACCAGGGCCGGA GCAGGAGTGGGGGGGCATCTATTGGTTTTCACACCCAAACCATCCTCATTCTCTCCCTCTCAGC CCTGGCCCTGCTTGGACCTCGATA GGTCCGACGGC ORF Start: ATG at 14                   ORF Stop: TAG at 1751 SEQ ID NO: 80           579 aa         MW at 62828.7 kD NOV15l, MSALRPLLLLLLPLCPGPGPCPGSEAKVTRSCAETRQVLGARGYSLNLIPPALISGEHLRVCPQ CG50970-07 Protein Sequence EYTCCSSETEQRLIRETEATFRGLVEDSGSFLVHTLAARHRKFDEFFLEMLSVAQHSLTQLFSH SYGRLYAQHALIFNGLFSRLRDFYGESGEGLDDTLADFWAQLLERVFPLLHPQYSFPPDYLLCL SRLASSTDGSLQPFGDSPRRLRLQITRTLVAARAFVQGLETGRNVVSEALKVPVSEGCSQALMR LIGCPLCRGVPSLMPCQGFCLNVVRGCLSSRGLEPDWGNYLDGLLILADKLQGPFSFELTAESI GVKISEGLMYLQENSAKVSAQVFQECGPPDPVPARNRRAPPPREEAGRLWSMVTEEERPTTAAG TNLHRLVWELRERLARMRGFWARLSLTVCGDSRMAADASLEAAPCWTGAGRGRYLPPVVGGSPA EQVNNPELKVDASGPDVPTRRRRLQLRAATARNKTAALGHDLDGQDADEDASGSGGGQQYADDW MAGAVAPPARPPRPPYPPRRDGSGGKCGGGSARYNQGRSRSGGASIGFHTQTILILSLSALALL GPR

[0424] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 15B. TABLE 15B Comparison of NOV15a against NOV15b through NOV15l. Identities/ Similarities for Protein NOV15a Residues/ the Matched Sequence Match Residues Region NOV15b 1 . . . 579  579/579 (100%) 1 . . . 579  579/579 (100%) NOV15c 1 . . . 579  579/579 (100%) 1 . . . 579  579/579 (100%) NOV15d 24 . . . 567  543/544 (99%) 4 . . . 547 544/544 (99%) NOV15e 1 . . . 391  391/391 (100%) 1 . . . 391  391/391 (100%) NOV15f 21 . . . 391  369/371 (99%) 2 . . . 372 369/371 (99%) NOV15g 21 . . . 391  369/371 (99%) 2 . . . 372 369/371 (99%) NOV15h 1 . . . 579  579/579 (100%) 5 . . . 583  579/579 (100%) NOV15i 1 . . . 380 379/380 (99%) 1 . . . 380 380/380 (99%) NOV15j 1 . . . 119 118/119 (99%) 1 . . . 119 119/119 (99%) NOV15k 24 . . . 553  528/530 (99%) 1 . . . 530 529/530 (99%) NOV15l 1 . . . 579  579/579 (100%) 1 . . . 579  579/579 (100%)

[0425] Further analysis of the NOV15a protein yielded the following properties shown in Table 15C. TABLE 15C Protein Sequence Properties NOV15a SignalP Cleavage site between residues 24 and 25 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 5; pos. chg 1; neg. chg 0 H-region: length 19; peak value 10.14 PSG score: 5.74 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −0.46 possible cleavage site: between 20 and 21 >>> Seems to have a cleavable signal peptide (1 to 20) ALOM: Klein et al's method for TM region allocation Init position for calculation: 21 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 4.24 (at 254) ALOM score: −0.85 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 10 Charge difference: −1.0 C(1.0)-N(2.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 8.46 Hyd Moment(95): 7.50 G content: 4 D/E content: 1 S/T content: 2 Score: −4.90 Gavel: indication of cleavage sites for mitochondrial preseq R-3 motif at 45 ARGY|S NUCDISC: discrimination of nuclear localization signals pat4: RHRK (3) at 103 pat4: RRRR (5) at 468 pat7: PRRLRLQ (5) at 210 pat7: PARNRRA (4) at 353 pat7: PTRRRRL (5) at 466 bipartite: none content of basic residues: 10.9% NLS Score: 1.23 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: SALR none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 55.5 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 33.3%: extracellular, including cell wall 33.3%: mitochondrial 22.2%: endoplasmic reticulum 11.1%: vacuolar >> indication for CG50970-06 is exc (k = 9)

[0426] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D. TABLE 15D Geneseq Results for NOV15a Identities/ Similarities for Geneseq Protein/Organism/Length NOV15a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value ABG70277 Human Glypican-2 Precursor-like 1 . . . 579  579/579 (100%) 0.0 protein #1 - Homo sapiens, 579 aa. 1 . . . 579  579/579 (100%) [WO200255702-A2, 18 JUL. 2002] ABG70279 Human Glypican-2 Precursor-like 1 . . . 391  391/391 (100%) 0.0 protein #3 - Homo sapiens, 449 aa. 1 . . . 391  391/391 (100%) [WO200255702-A2, 18 JUL. 2002] ABG70278 Human Glypican-2 Precursor-like 1 . . . 380 378/380 (99%) 0.0 protein #2 - Homo sapiens, 465 aa. 1 . . . 380 379/380 (99%) [WO200255702-A2, 18 JUL. 2002] AAU29071 Human PRO polypeptide 2 . . . 511 227/512 (44%) e−127 sequence #48 - Homo sapiens, 7 . . . 504 329/512 (63%) 555 aa. [WO200168848-A2, 20 SEP. 2001] AAB44256 Human PRO705 (UNQ369) protein 2 . . . 511 227/512 (44%) e−127 sapiens, 555 aa. [WO200053756-A2, 7 . . . 504 329/512 (63%) 14 SEP. 2000]

[0427] In a BLAST search of public sequence databases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15E. TABLE 15E Public BLASTP Results for NOV15a Identities/ Protein Similarities for Accession NOV15a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value Q8N158 Similar to cerebroglycan 1 . . . 579  579/579 (100%) 0.0 (Hypothetical protein FLJ38962) - 1 . . . 579  579/579 (100%) Homo sapiens (Human), 579 aa. P51653 Glypican-2 precursor 1 . . . 579 477/581 (82%) 0.0 (Cerebroglycan) (HSPG M13) - 1 . . . 579 513/581 (88%) Rattus norvegicus (Rat), 579 aa. Q9R087 Glypican-6 precursor - Mus musculus 2 . . . 511 227/512 (44%) e−127 (Mouse), 555 aa. 7 . . . 504 332/512 (64%) Q9Y625 Glypican-6 precursor - Homo sapiens 2 . . . 511 227/512 (44%) e−127 (Human), 555 aa. 7 . . . 504 329/512 (63%) Q8R3X6 Similar to glypican 6 - Mus musculus 2 . . . 511 228/522 (43%) e−125 (Mouse), 565 aa. 7 . . . 514 333/522 (63%)

[0428] PFam analysis indicates that the NOV15a protein contains the domains shown in the Table 15F. TABLE 15F Domain Analysis of NOV15a NOV15a Identities/ Pfam Match Similarities for Expect Domain Region the Matched Region Value Glypican 3 . . . 566 271/631 (43%) 6.7e−291 510/631 (81%)

Example 16

[0429] The NOV 16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A. TABLE 16A NOV16 Sequence Analysis SEQ ID NO: 81          1242 bp NOV16a, ATGGGGTCGACCGACTCCAAGCTGAACTTCCGGAAGGCGGTGATCCAGCTCACCACCAAGACGCA CG54443-03 DNA Sequence GCCCGTGGAAGCCACCGATGATGCCTTTTGGGACCAGTTCTGGGCAGACACAGCCACCTCGGTGC AGGATGTGTTTGCACTGGTGCCGGCAGCAGAGATCCGGGCCGTGCGGGAAGAGTCACCCTCCAAC TTGGCCACCCTGTGCTACAAGGCCGTTGAGAGGCTGGTGCAGGGAGCTGAGAGTGGCTGCCACTC GGAGAACGAGAAGCAGATCGTCCTGAACTGCAGCCGGCTGCTCACCCGCGTGCTGCCCTACATCT TTGAGGACCCCGACTGGAGGGGGCTTCTTCTGGTCCCAGTGCCCGGGGCAGGGCGAGGAGGGCAG GGAGAAGAGGATGATCAGCATGCCAGGCCCCTGGCCGAGTCCCTGCTCCTGGCCATTGCTGACCT GCTCTTCTGCCCGGACTTCACGGTTCAGAGCCACCGGAGGAGCACTGTGGACTCGGCAGAGGACG TCCACTCCCTGGACAGCTGTGAATACATCTGGGAGGCTGGTGTGGGCTTCGCTCACTCCCCCCAG CCTAACTACATCCACGATATGAACCGGATGGAGCTGCTGAAACTGCTGCTGACATGCTTCTCCGA GGCCATGTACCTGCCCCCAGCTCCGGAAAGTGGCAGCACCAACCCATGGGTTCAGTTCTTTTGTT CCACGGAGAACAGACATGCCCTGCCCCTCTTCACCTCCCTCCTCAACACCGTGTGTGCCTATGAC CCTGTGGGCTACGGGATCCCCTACAACCACCTGCTCTTCTCTGACTACCGGGAACCCCTGGTGGA GGAGGCTGCCCAGGTGCTCATTGTCACTTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTG TGGACGGCACCACCACTGGCACCGCCATGGATGATGCCGATCCTCCAGGCCCTGAGAACCTGTTT GTGAACTACCTGTCCCGCATCCATCGTGAGGAGGACTTCCAGTTCATCCTCAAGGGTATAGCCCG GCTGCTGTCCAACCCCCTGCTCCAGACCTACCTGCCTAACTCCACCAAGAAGATCCAGTTCCACC AGGAGCTGCTAGTTCTCTTCTGGAAGCTCTGCGACTTCAACAAGAAATTCCTCTTCTTCGTGCTG AAGAGCAGCGACGTTCCTAGACATCCTTGTCCCCATCCTCTTCTTCCTCAACGATGCCGGGCCGA TCAGTCT ORF Start: ATG at 1                    ORF Stop: end of sequence SEQ ID NO: 82           414 aa         MW at 46487.9 kD NOV16a, MGSTDSKLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVREESPS CG54443-03 Protein Sequence NLATLCYKAVERLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWSTVPGAGRG GQGEEDDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSCEYIWEAGVGFAH SPQPNYIHDMNRMELLKLLLTCFSEAMYLPPAPESGSTNPWVQFFCSTENRHALPLFTSLLNTV CAYDPVGYGIPYNHLLFSDYREPLVEEAAQVLIVTLDHDSASSASPTVDGTTTGTAMDDADPPG PENLFVNYLSRIHREEDFQFILKGIARLLSNPLLQTYLPNSTKKIQFHQELLVLFWKLCDFNKK FLFFVLKSSDVLDILVPTLFFLNDARADQS SEQ ID NO: 83          1912 bp NOV16b, CGAGCGCCGGGGGCCGGGCGCGCCGCTTGTCTCCTGCGAGAGCCGCGGGGGCCGCGGAGCTGGA CG54443-07 DNA Sequence GCCGGAGCTGAAGCCCGAGCCGGGTTGGAGTCTTGGGCGGGGGCCGGGCCGGAGCCGGCTCCAG AGAC ATGGGTCGACCGACTCCGCTGAACTTCCGGAAGGCGGTGATCCAGCTCACCACCACCAAG ACGCAGCCCGTGGAAGCCACCGATGATGCCTATGACCCTGTGGGCTACGGGATCCCCTACAACC ACCTGCTCTTCTCTGACACCGGGGAACCCCTGGTGGAGGAGGCTGCCCAGGTGCTCATTGTCAC TTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTGTGGACGGCACCACCACTGGCACCGCC ATGGATGATGCCGATCCTCCAGGCCCTGAGAACCTGTTTGTGAACTACCTGTCCCGCATCCATC GTGAGGAGGACTTCCAGTTCATCCTCAAGGGTATAGCCCGGCTGCTGTCCAACCCCCTGCTCCA GACCTACCTGCCTAACTCCACCAAGAAGATCCAGTTCCACCACGAGCTGCTAGTTCTCTTCTGG AAGCTCTGCCACTTCAACAAGAAATTCCTCTTCTTCGTGCTGAAGAGCAGCGACGTCCTAGACA TCCTTGTCCCCATCCTCTTCTTCCTCAACGATGCCCGGGCCGATCAGTCTCGGGTGGGCCTGAT GCACATTGGTGTCTTCATCTTGCTGCTTCTGAGCGGGGAGCGGAACTTCCGGGTGCGGCTGAAC AAACCCTACTCAATCCGCGTGCCCATGGACATCCCAGTCTTCACAGGGACCCACGCCGACCTGC TCATTGTGGTGTTCCACAAGATCATCACCAGCGGGCACCAGCCGTTGCAGCCCCTCTTCGACTG CCTGCTCACCATCGTGGTCAACGTGTCCCCCTACCTCAAGAGCCTGTCCATGGTGACCGCCAAC AAGTTGCTGCACCTGCTGGAGGCCTTCTCCACCACCTGCTTCCTCTTCTCTGCCGCCCAGAACC ACCACCTGGTCTTCTTCCTCCTCGAGGTCTTCAACAACATCATCCAGTACCAGTTTGATGGCAA CTCCAACCTGGTCTACGCCATCATCCCCAAGCGCAGCATCTTCCACCAGCTCGCCAACCTGCCC ACGGACCCGCCCACCATTCACAAGGCCCTGCAGCGGCGCCGGCGGACACCTGAGCCCTTGTCTC GCACCGGCTCCCAGCAGCGCACCTCCATGGAGGGCTCCCGCCCCGCTGCCCCTGCAGAGCCAGG CACCCTCAAGACCAGTCTGGTGGCTACTCCACGCATTGACAAGCTGACCGAGAAGTCCCAGGTG TCAGAGGATGGCACCTTGCGGTCCCTGGAACCTGAGCCCCAGCAGAGCTTGGAGGATGGCAGCC CGGCTAAGGGGGAGCCCAGCCCGGCATGGAGGGAGCAGCGGCGACCATCCACCTCATCAGCCAG TCGGCAGTGGAGCCCAACGCCAGAGTGGGTCCTCTCCTGGAAGTCGAAGCTGCCGCTGCAGACC ATCATCAGGCTGCTGCAGGTGCTGGTTCCGCAGGTGGAGAAGTCTGCATCGAACAAGGGCCTGA CGGATGAGTCTGAGATCCTGCGGTTCCTGCAGCATGGCACCCTGGTGGGGCTGCTGCCCGTGCC CCACCCCATCCTCATCCGCAAGTACCAGGCCCACTCGGGCACTGCCATGTGGTTCCGCACCTAC ATGTGGGGCGTCATCTATCTGAGGAATGTGGACCCCCCTGTCTGGTACGACACCGACGTGAAGC TGTTTGAGATACAGCGGGTGTGA GGATGAAGCCGACGAGGGGCTCAGTCTAGCGGAAGGCAGGG CCTTGGTCCCTGAGGCTTCCCCCATCCACCATTCTGAGCTTTAAATTACCACGATC ORF Start: ATG at 133                  ORF Stop: TGA at 1813 SEQ ID NO: 84           560 aa         MW at 63082.9 kD NOV16b, MGSTDSKLNFRKAVIQLTTKTQPVEATDDAYDPVGYGIPYNHLLFSDTGEPLVEEAAQVLIVTL CG54443-07 Protein Sequence DHDSASSASPTVDGTTTGTAMDDADPPGPSNLFVNYLSRIHREEDFQFILKGIARLLSNPLLQT YLPNSTKKIQFHQELLVLFWKLCDFNKKFLFFVLKSSDVLDTLVPILFFLNDARADQSRVGLMH IGVFILLLLSGERNFGVRLNKPYSIRVPMDIPVFTGTHADLLIVVFHKIITSGHQRLQPLFDCL LTIVVNVSPYLKSLSMVTANKLLHLLEAFSTTWFLFSAAQNHHLVFFLLEVFNNTTQYQFDGNS NLVYAIIRKRSIFHQLANLPTDPPTIHKALQRRRRTPEPLSRTGSQEGTSMEGSRPAAPAEPGT LKTSLVATPGIDKLTEKSQVSEDGTLRSLEPEPQQSLEDGSPAKGEPSQAWREQRRPSTSSASG QWSPTPEWVLSWKSKLPLQTIMRLLQVLVPQVEKICIDKGLTDESEILRFLQHGTLVGLLPVPM PILIRKYQANSGTAMWPRTYMWGVIYLRNVDPPVWYDTDVKLFEIQRV SEQ ID NO: 85          3146 bp NOV16c, ATGGGGTCGACCGACTCCAAGCTGAACTTCCGGAAGGCGGTGATCCAGCTCACCACCAAGACGC CG54443-01 DNA Sequence AGCCCGTGGAAGCCACCGATGATGCCTTTTGGGACCAGTTCTGGGCAGACACAGCCACCTCGGT GCAGGATGTGTTTGCACTGGTGCCGGCAGCAGAGATCCGGGCCGTGCGGGAAGAGTCACCCTCC AACTTGGCCACCCTGTGCTACAAGGCCGTTGAGAAGCTGGTGCAGGGAGCTGAGAGTGGCTGCC ACTCCGAGAAGGAGAAGCAGATCGTCCTGAACTGCAGCCCGCTGCTCACCCGCGTGCTGCCCTA CATCTTTGAGGACCCCGACTGGAGGGGCTTCTTCTGGTCCACAGTGCCCCAGCAGGGAGAAGAG GATGATGAGCATGCCAGGCCCCTGGCCGAGTCCCTGCTCCTGGCCATTGCTGACCTGCTCTTCT GCCCGGACTTCACGGTTCAGAGCCACCGGACGAGCACTGTGGACTCGGCAGAGGACGTCCACTC CCTGGACAGCTGTGAATACATCTGGGAGGCTGGTGTGGGCTTCGCTCACTCCCCCCAGCCTAAC TACATCCACGATATGAACCGGATGGAGCTGCTGAAACTGCTGCTGACATGCTTCTCCGAGGCCA TGTACCTGCCCCCAGCTCCGGAAAGTGGCAGCACCAACCCATGGGTTCAGTTCTTTTGTTCCAC GGAGAACAGACATGCCCTGCCCCTCTTCACCTCCCTCCTCAACACCGTGTGTGCCTATGACCCT GTGGGCTACGGGATCCCCTACAACCACCTGCTCTTCTCTGACTACCCGGAACCCCTGGTGGAGG AGGCTGCCCAGGTGCTCATTGTCACTTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTGT GGACGGCACCACCACTGGCACCGCCATGGATGATGCCGATGACTTCCAGTTCATCCTCAAGGGT ATAGCCCGGCTGCTGTCCAACCCCCCTGCTCCAGACCTACCTGCCTAACTCACCAAGAAGATCC AGTTCCACCAGGAGCTGCTAGTTCTCTTCTGCAAGCTCTGCGACTTCAACAAGAAATTCCTCTT CTTCGTGCTGAAGAGCAGCGACGTCCTAGACATCCTTGTCCCCATCCTCTTCTTCCTCAACGAT GCCCGGGCCGATCAGTCTCGGGTGGGCCTGATGCACATTGGTGTCTTCATCTTGCTGCTTCTGA GCGGGGAGCGGAACTTCGGGGTGCGGCTGAACAAACCCTACTCAATCCGCGTGCCCATGGACAT CCCAGTCTTCACAGGGACGCACGCCGACCTGCTCATTGTGGTGTTCCACAAGATCATCACCAGC GGGCACCAGCGGTTGCAGCCCCTCTTCGACTGCCTGCTCACCATCGTCGTCAACGTGTCCCCCT ACCTCAAGAGCCTGTCCATGGTGACCGCCAACAAGTTGCTGCACCTGCTGGAGGCCTTCTCCAC CACCTGGTTCCTCTTCTCTGCCGCCCAGAACCACCACCTGGTCTTCTTCCTCCTGGACGTCTTC AACAACATCATCCAGTACCAGTTTGATGGCAACTCCAACCTGGTCTACGCCATCATCCGCAAGC GCAGCATCTTCCACCAGCTGGCCAACCTGCCCACGGACCCGCCCACCATTCACAAGGCCCTGCA GCGGCGCCGGCGGACACCTGAGCCCTTGTCTCGCACCGGCTCCCAGGAGGGCACCTCCATGGAG GGCTCCCGCCCCGCTGCCCCTGCAGAGCCAGGCACCCTCAAGACCAGTCTGGTGGCTACTCCAG GCATTGACAAGCTGACCGAGAAGTCCCAGGTGTCAGAGGATGGCACCTTGCGGTCCCTGGAACC TGAGCCCCAGCAGAGCTTGGAGGATGGCAGCCCGGCTAAGGGGGAGCCCAGCCAGGCATGGAGG GAGCAGCGGCGACCGTCCACCTCATCAGCCAGTGGGCAGTGGAGCCCAACGCCAGAGTGGGTCC TCTCCTGGAAGTCGAAGCTGCCGCTGCAGACCATCATGAGGCTGCTGCAGGTGCTGGTTCCGCA GGTGGAGAAGATCTGCATCGACAAGGGCCTGACGGATGAGTCTGAGATCCTGCGGTTCCTGCAG CATGGCACCCTCGTGGGGCTGCTGCCCGTGCCCCACCCCATCCTCATCCGCAAGTACCAGGCCA ACTCGGGCACTGCCATGTGGTTCCGCACCTACATGTGGGGCGTCATCTATCTGAGGAATGTGGA CCCCCCTGTCTGGTACGACACCGACGTGAAGCTGTTTGAGATACAGCGGGTGTGA GGATGAAGC CGACGAGGGGCTCAGTCTAGGGGAAGGCAGGGCCTTGGTCCCTGAGGCTTCCCCCATCCACCAT TCTGAGCTTTAAATTACCACGATCAGGGCCTGGAACAGGCAGAGTGGCCCTGAGTGTCATGCCC TAGAGACCCCTGTGGCCAGGACAATGTGAACTGGCTCAGATCCCCCTCAACCCCTAGGCTGGAC TCACAGGAGCCCCATCTCTGGCGCTATGCCCCCACCAGAGACCACTGCCCCCAACACTCGGACT CCCTCTTTAAGACCTGGCTCAGTGCTGGCCCCTCAGTGCCCACCCACTCCTGTGCTACCCAGCC CCAGAGGCAGAAGCCAAAATGGGTCACTGTGCCCTAAGGGGTTTGACCAGGGAACCACGGGCTG TCCCTTGAGGTGCCTGGACAGGGTAAGGGGGTGCTTCCAGCCTCCTAACCCAAAGCCAGCTGTT CCAGGCTCCAGGGGAAAAAGGTGTGGCCAGGCTCCTCCTCGACGAGGCTGGGAGCTGGCCGACT GCAAAAGCCAGACTGGGGCACCTCCCGTATCCTTGGGGCATGGTGTGGGGTGGTGAGAGTCTCC TGCTATATTCTCCTGGATCCATGGAAATAGCCTGGCTCCCTCTTACCCAGTAATGAGGGGCAGG GAAGGGACTGGAGGCAGCCGTTTAGTCCTCCCCTGCCCTGCCCACTGCCCTGGATGGGGCGATG CCACCCCTCATCCTTCACCCAGCTCTGGCCTCTGGGTCCCACCACCCAGCCCCCCGTGTCAGAA CAATCTTTGCTCTGTACAATCGGCCTCTTTACAATAAAACCTCCTGCTCCAAAAAAAAAAAAAA AAAAAAAAAA ORF Start: ATG at 1                    ORF Stop: TGA at 2293 SEQ ID NO: 86           764 aa         MW at 86166.6 kD NOV16c, MQSTDSCLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVREESPS CG54443-01 Protein Sequence NLATLCYKAVEKLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWSTVPQQGEE DDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSCEYIWEAGVGFAHSPQPN YIHDMNRMELLKLLLTCFSEAMYLPPAPESGSTNPWVQFFCSTENRHALPLFTSLLNTVCAYDP VGYGIPYNHLLFSDYREPLVEEAAQVLIVTLDHDSASSASPTVDGTTTGTAMDDADDFQFILKG IARLLSNPLLQTYLPNSTKKIQFHQELLVLFWKLCDFNKKFLFFVLKSSDVLDILVPILFFLND ARADQSRVGLMHIGVFILLLLSGERNFGVRLNKPYSIRVPMDIPVFTGTHADLLIVVFHKIITS GHQRLQPLFDCLLTIVVNVSPYLKSLSMVTANKLLHLLEAFSTTWFLFSAAQNHHLVFFLLEVF NNIIQYQFDGNSNLVYAIIRKRSIFHQLANLPTDPPTIHKALQRRRRTPEPLSRTGSQEGTSME GSRPAAPAEPGTLKTSLVATPGIDKLTEKSQVSEDGTLRSLEPEPQQSLEDGSPAKGEPSQAWR EQRRPSTSSASGQWSPTPEWVLSWKSKLPLQTIMRLLQVLVPQVEKICIDKGLTDESEILRFLQ HGTLVGLLPVPHPILIRKYQANSGTANWFRTYMWGVIYLRNVDPPVWYDTDVKLFEIQRV SEQ ID NO: 87          3314 bp NOV16d, GCGAGAGCCGCGGGGGCCGCGGAGCTGGAGCCGGAGCTGAAGCCGGAGCCGGGTTGGAGTCTGG CG54443-02 DNA Sequence GCGGGGGCCGGGCCGGAGCGGGCTCCAGAGAC ATGGGGTCGACCGACTCCAAGCTGAACTTCCG GAAGGCGGTGATCCAGCTCACCACCAAGACGCAGCCCGTCGAAGCCACCGATGATGCCTTTTGG GACCAGTTCTGGGCAGACACAGCCACCTCGGTGCAGGATGTGTTTGCACTGGTGCCGGCAGCAG AGATCCCGGCCGTGCGGGAAGAGTCACCCTCCAACTTGGCCACCCTGTGCTACAAGGCCGTTGA GAAGCTGGTGCAGGGAGCTGAGAGTGGCTGCCACTCCGAGAAGGAGAAGCAGATCGTCCTGAAC TGCAGCCGGCTGCTCACCCGCGTGCTGCCCTACATCTTTGAGGACCCCGACTCGAGGGGCTTCT TCTCGTCCACAGTGCCCGGGGCACGGCGAGGAGGGCAGGGAGAAGAGGATGATGAGCATGCCAG GCCCCTCGCCGAGTCCCTGCTCCTGGCCATTGCTGACCTGCTCTTCTGCCCGGACTTCACGGTT CAGAGCCACCGGAGGAGCACTGTGGACTCGGCAGAGGACGTCCACTCCCTGGACAGCTGTGAAT ACATCTGGGAGGCTCGTGTCGGCTTCGCTCACTCCCCCCAGCCTAACTACATCCACGATATGAA CCGGATGGAGCTGCTGAAACTGCTGCTGACATGCTTCTCCGAGGCCATGTACCTGCCCCCAGCT CCGGAAAGTCGCAGCACCAACCCATGGGTTCAGTTCTTTTGTTCCACGGAGAACAGACATGCCC TGCCCCTCTTCACCTCCCTCCTCAACACCGTGTGTGCCTATGACCCTGTGGGCTACGGGATCCC CTACAACCACCTGCTCTTCTCTGACACCGGGGAACCCCTGGTGGAGGAGGCTGCCCAGGTGCTC ATTGTCACTTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTGTGGACGGCACCACCACTG GCACCGCCATGGATGATGCCGATCCTCCAGGCCCTGAGAACCTGTTTGTGAACTACCTGTCCCG CATCCATCGTGAGGAGGACTTCCAGTTCATCCTCAAGGGTATAGCCCGGCTGCTGTCCAACCCC CTGCTCCAGACCTACCTGCCTAACTCCACCAAGAAGATCCAGTTCCACCAGGAGCTGCTAGTTC TCTTCTCGAAGCTCTGCGACTTCAACAAGAAATTCCTCTTCTTCGTGCTGAAGAGCAGCGACGT CCTAGACATCCTTGTCCCCATCCTCTTCTTCCTCAACGATGCCCGGGCCGATCAGTCTCGGGTG GGCCTGATGCACATTCGTGTCTTCATCTTGCTGCTTCTGAGCGGGGAGCGGAACTTCGGGGTGC GCCTGAACAAACCCTACTCAATCCGCGTGCCCATGGACATCCCAGTCTTCACAGGGACCCACGC CGACCTGCTCATTGTGGTGTTCCACAAGATCATCACCAGCGGGCACCAGCGGTTGCAGCCCCTC TTCGACTGCCTGCTCACCATCGTCGTCAACGTGTCCCCCTACCTCAAGAGCCTGTCCATGGTGA CCGCCAACAAGTTGCTGCACCTGCTGGACGCCTTCTCCACCACCTGGTTCCTCTTCTCTGCCGC CCAGAACCACCACCTGGTCTTCTTCCTCCTGGAGGTCTTCAACAACATCATCCAGTACCAGTTT GATGGCAACTCCAACCTGGTCTACGCCATCATCCGCAAGCGCAGCATCTTCCACCAGCTGGCCA ACCTGCCCACGGACCCGCCCACCATTCACAAGGCCCTGCAGCGGCGCCGGCGGACACCTGAGCC CTTGTCTCGCACCGGCTCCCAGGAGGGCACCTCCATGGACGGCTCCCGCCCCGCTGCCCCTGCA GAGCCAGGCACCCTCAAGACCCAGTCTGGTGGCTACTCCAGGGCATTGACAAGCTGACCGAAGT CCCAGGTGTCAGAGGATGGCACCTTGCGGTCCCTGGAACCTGAGCCCCAGCAGAGCTTGGAGGA TGGCAGCCCCGCTAAGGCGGAGCCCAGCCAGGCATGGAGGGAGCAGCGGCGACCATCCACCTCA TCAGCCAGTGGGCAGTGGAGCCCAACGCCAGAGTGGGTCCTCTCCTGGAAGTCGAAGCTGCCGC TGCAGACCATCATGAGGCTGCTGCAGGTGCTGGTTCCGCAGGTGGAGAAGATCTGCATCGACAA GGGCCTGACGGATGAGTCTGAGATCCTGCGGTTCCTGCAGCATGGCACCCTGGTGGGGCTGCTG CCCGTGCCCCACCCCATCCTCATCCGCAAGTACCAGGCCAACTCGGGCACTGCCATGTGGTTCC GCACCTACATGTGGGGCGTCATCTATCTGAGGATGTGGACCCCCCCTGTCTCGTACGACACCGA CGTGAAGCTGTTTGAGATACAGCGGGTGTGA GGATGAAGCCGACGAGGGGCTCAGTCTAGGGGA AGGCAGGGCCTTCGTCCCTGAGGCTTCCCCCATCCACCATTCTGAGCTTTAAATTACCACGATC AGGGCCTGGAACAGGCAGAGTGGCCCTGAGTGTCATGCCCTACAGACCCCTGTGGCCAGGACAA TGTGACTGGCTCAGATCCCCCTCAACCCCTAGGCTGGGACTCACAGGAGCCCCATCTCTCGGGC TATGCCCCCACCAGAGACCACTGCCCCCAACACTCCGACTCCCTCTTTAAGACCTGGCTCAGTG CTGGCCCCTCAGTGCCCACCCACTCCTGTGCTACCCAGCCCCAGAGGCAGAAGCCAAAATGGGT CACTGTGCCCTAAGGGTTTGACCAGGGAAACCACGGGCTGTCCCTTGAGGTGCCTGGACAGGGT AAGGGGGTGCTTCCAGCCTCCTAACCCAAAGCCAGCTGTTCCAGGCTCCAGGGGAAAAAGGTGT GGCCAGGCTGCTCCTCGAGGAGGCTGGGAGCTGGCCGACTGCAAAAGCCAGACTGGGGCACCTC CCGTATCCTTGGGOCATGGTGTCGGGTGGTGAGGGTCTCCTGCTATATTCTCCTGGATCCATGG AAATAGCCTGGCTCCCTCTTACCCAGTAATGAGGGGCAGGGAAGGGAACTGGGAGGCAGCCGTT TAGTCCTCCCTGCCCTGCCCACTGCCTGGATGGCGCGATGCCACCCCTCATCCTTCACCCAGCT CTGGCCTCTGGGTCCCACCACCCAGCCCCCCGTGTCAGAACAATCTTTGCTCTGTACAATCGGC CTCTTTACATAAAACCTCCTGCTCCAAAAAAAAAAAAAAAAAAAAAAAAA ORF Start: ATG at 97                   ORF Stop: TGA at 2461 SEQ ID NO: 88           788 aa         MW at 88582.2 kD NOV16d, MGSTDSKLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVREESPS CG54443-02 Protein Sequence NLATLCYKAVEKLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWSTVPGAGRG GQGEEDDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSCEYIWEAGVGFAH SPQPNYIHDMNRMELLKLLLTCFSEAMYLPPAPESGSTNPWVQFFCSTENRHALPLFTSLLNTV CAYDPVGYGIPYNMLLFSDTGEPLVEEAAQVLIVTLDHDSASSASPTVDGTTTGTAMDDADPPG PENLFVNYLSRIHREEDFQFILKGIARLLSNPLLQTYLPNSTKKIQFHQELLVLFWKLCDFNKK WLFFVLKSSDVLDILVPILFFLNDARADQSRVGLMHIGVFILLLLSGERNFGVRLNKPYSIRVP MDIPVFTGTHADLLIVVFHKIITSCHQRLQPLFDCLLTIVVNVSPYLKSLSMVTANKLLHLLEA FSTTWFLFSAAQNHHLVFFLLEVFNNIIQYQFDGNSNLVYAIIRKRSIFHQLANLPTDPPTIHK ALQRRRRTPEPLSRTGSQEGTSMEGSRPAAPAEPGTLKTSLVATPGIDKLTEKSQVSEDGTLRS LEPEPQQSLEDGSPAKGEPSQAWREQRRPSTSSASGQWSPTPEWVLSWKSKLPLQTIMRLLQVL VPQVEKICIDKGLTDESEILRFLQHGTLVGLLPVPHPILIRKYOANSGTAMWFRTYMWGVIYLR NVDPPVWYDTDVKLFEIQRV SEQ ID NO: 89          1242 bp NOV16e, ATGGGGTCGACCGACTCCAAGCTCAACTTCCGGAAGGCGGTGATCCAGCTCACCACCAAGACGCA CG54443-04 DNA Sequence GCCCGTGGAAGCCACCGATGATGCCTTTTGGGACCAGTTCTGGGCAGACACAGCCACCTCGGTGC AGGATGTGTTTGCACTGGTGCCGGCAGCAGAGATCCGGGCCGTGCGGGAAGAGTCACCCTCCAAC TTGGCCACCCTGTGCTACAAGGCCGTTGAGAGGCTGGTGCAGGGAGCTGAGAGTGGCTGCCACTC GGAGAAGGAGAAGCAGATCGTCCTGAACTGCAGCCGGCTGCTCACCCGCGTGCTGCCCTACATCT TTGAGGACCCCGACTGGAGGGGCTTCTTCTGGTCCACAGTGCCCGGGGCAGGGCGAGGAGGGCAG GGAGAAGAGGATGATGAGCATGCCAGGCCCCTGGCCGAGTCCCTGCTCCTGGCCATTGCTGACCT GCTCTTCTGCCCGGACTTCACGGTTCAGAGCCACCGGAGGAGCACTGTGGACTCGGCAGAGGACG TCCACTCCCTGGACAGCTGTGAATACATCTGGGAGGCTGGTGTGGGCTTCGCTCACTCCCCCCAG CCTAACTACATCCACGATATGAACCGGATGGAGCTGCTGAAACTGCTGCTGACATGCTTCTCCGA GGCCATGTACCTGCCCCCAGCTCCGGAAAGTGGCAGCACCAACCCATGGGTTCAGTTCTTTTGTT CCACGGAGAACAGACATGCCCTGCCCCTCTTCACCTCCCTCCTCAACACCGTGTGTGCCTATGAC CCTGTGGGCTACGGGATCCCCTACAACCACCTGCTCTTCTCTGACTACCGGGAACCCCTGGTGGA GGAGGCTGCCCAGGTGCTCATTGTCACTTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTG TGGACGGCACCACCACTGGCACCGCCATGGATGATGCCGATCCTCCAGGCCCTGAGAACCTGTTT GTGAACTACCTGTCCCGCATCCATCGTGAGGAGGACTTCCAGTTCATCCTCAAGGGTATAGCCCG GCTGCTGTCCAACCCCCTGCTCCAGACCTACCTGCCTAACTCCACCAAGAAGATCCAGTTCCACC AGGAGCTGCTAGTTCTCTTCTGGAAGCTCTGCGACTTCAACAAGAAATTCCTCTTCTTCGTGCTG AAGAGCAGCGACGTCCTAGACATCCTTGTCCCCATCCTCTTCTTCCTCAACGATGCCCGGGCCGA TCAGTCT ORF Start: ATG at 1                    ORF Stop: end of sequence SEQ ID NO: 90           414 aa         MW at 46487.9 kD NOV16e, MGSTDSKLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVREESPS CG54443-04 Protein Sequence NLATLCYKAVERLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWSTVPGAGRG GQGEEDDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSCEYIWEAGVGFAH SPQPNYIHDMNRMELLKLLLTCFSEAMYLPPAPESCSTNPWVQFFCSTENRHALPLFTSLLNTV CAYKPVGYGIPYNHLLFSDYREPLVEEAAQVLIVTLDHDSASSASPTVDGTTTGTAMDDADPPG PENLFVNYLSRIHREEDFQFILKGIARLLSNPLLQTYLPNSTKKIQFHQELLVLFWKLCDFNKK FLFFVLKSSDVLDILVPILFFLNDARADQS SEQ ID NO: 91          1242 bp NOV16f, ATGGGGTCGACCGACTCCAAGCTGAACTTCCGGAAGGCGGTGATCCAGCTCACCACCAAGACGCA CG54443-05 DNA Sequence GCCCGTGGAAGCCACCGATGATGCCTTTTGGGACCAGTTCTGGGCAGACACAGCCACCTCGGTGC AGGATGTGTTTGCACTGGTGCCGGCAGCAGAGATCCGGGCCGTGCGGGAAGAGTCACCCTCCAAC TTGGCCACCCTGTGCTACAAGGCCGTTGAGAGGCTGGTGCAGGGAGCTGAGAGTGGCTGCCACTC GGAGAACGAGAAGCAGATCGTCCTGAACTGCAGCCCGCTGCTCACCCGCGTGCTGCCCTACATCT TTGAGGACCCCGACTGGAGGGGCTTCTTCTGGTCCACAGTGCCCGGGGCAGGGCGAGGAGGGCAG GGAGAAGAGGATGATGAGCATGCCAGGCCCCTGGCCGAGTCCCTGCTCCTGGCCATTGCTGACCT GCTCTTCTGCCCGGACTTCACGGTTCAGAGCCACCGGAGGAGCACTGTGGACTCGGCAGAGGACG TCCACTCCCTGGACAGCTGTGAATACATCTGGGAGGCTGGTGTGGGCTTCGCTCACTCCCCCCAG CCTAACTACATCCACGATATGAACCGGATGGAGCTGCTGAAACTGCTGCTGACATGCTTCTCCGA GGCCATGTACCTGCCCCCAGCTCCGGAAAGTGGCAGCACCAACCCATGGGTTCAGTTCTTTTGTT CCACGGAGAACAGACATGCCCTGCCCCTCTTCACCTCCCTCCTCAACACCGTGTGTGCCTATGAC CCTGTGGGCTACGGGATCCCCTACAACCACCTGCTCTTCTCTGACTACCGGGAACCCCTGGTGGA GGAGGCTGCCCAGGTGCTCATTGTCACTTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTG TCGACGGCACCACCACTGGCACCGCCATCGATGATGCCGATCCTCCAGGCCCTGAGAACCTGTTT GTGAACTACCTGTCCCGCATCCATCGTGAGGAGGACTTCCAGTTCATCCTCAAGGGTATAGCCCG GCTGCTGTCCAACCCCCTGCTCCAGACCTACCTGCCTAACTCCACCAAGAAGATCCAGTTCCACC AGGAGCTGCTAGTTCTCTTCTGGAAGCTCTGCGACTTCAACAAGAAATTCCTCTTCTTCGTGCTG AAGAGCAGCGACGTCCTAGACATCCTTGTCCCCATCCTCTTCCTTCCTCAACGATGCCCGGCCGA TCAGTCT ORF Start: ATG at 1                    ORF Stop: end of sequence SEQ ID NO: 92           414 aa         MW at 46487.9 kD NOV16f, MGSTDSKLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVREESPS CG54443-05 Protein Sequence NLATLCYKAVERLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWSTVPGAGRG GQGEEDDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSCEYIWEAGVGFAH SPQPNYIHDMNRMELLKLLLTCFSEANYLPPAPESGSTNPNVQFFCSTENRHALPLFTSLLNTV CAYDPVGYGIPYNHLLFSDYREPLVEEAAQVLIVTLDHDSASSASPTVDGTTTGTAMDDADPPG PENLFVYLSRIHREEDFQFILKGIARLLSNPLLQTYLPNSTKKIQFHQELLVLFWKLCDFNKK FLFFVLKSSDVLDILVPILFFLNDARADQS SEQ ID NO: 93          1242 bp NOV16g, ATGGGGTCGACCGACTCCAAGCTGAACTTCCGGAAGGCGGTGATCCAGCTCACCACCAAGACGCA CG54443-06 DNA Sequence GCCCGTGGAAGCCACCGATGATGCCTTTTGGGACCAGTTCTGGGCAGACACAGCCACCTCGGTGC AGGATGTGTTTGCACTGGTGCCGGCAGCAGAGATCCGGGCCGTGCGGGAAGAGTCACCCTCCAAC TTGGCCACCCTGTGCTACAACGCCGTTGAGAGGCTGGTGCAGGGAGCTGAGAGTCGCTGCCACTC GGAGAACGAGAAGCAGATCGTCCTGAACTGCAGCCGGCTGCTCACCCGCGTGCTGCCCTACATCT TTGAGGACCCCGACTGGAGGGGCTTCTTCTGGTCCACAGTGCCCGGGGCAGGGCGAGGAGGGCAG GGAGAAGAGGATGATGAGCATGCCACGCCCCTGGCCGAGTCCCTGCTCCTGGCCATTGCTGACCT GCTCTTCTGCCCGGACTTCACGGTTCAGAGCCACCGGAGGAOCACTGTGGACTCGGCAGAGGACG TCCACTCCCTGGACAGCTGTGAATACATCTGGGAGGCTGGTGTGGGCTTCGCTCACTCCCCCCAG CCTAACTACATCCACGATATGAACCGGATGGAGCTGCTGAAACTGCTGCTGACATGCTTCTCCGA GGCCATGTACCTGCCCCCAGCTCCGGAAAGTGGCAGCACCAACCCATGGGTTCAGTTCTTTTGTT CCACGGAGAACAGACATGCCCTGCCCCTCTTCACCTCCCTCCTCAACACCGTGTGTGCCTATGAC CCTGTGGGCTACGGGATCCCCTACAACCACCTGCTCTTCTCTGACTACCGGGAACCCCTGGTGGA GGAGGCTGCCCAGGTGCTCATTGTCACTTTGGACCACGACAGTGCCAGCAGTGCCAGCCCCACTG TGGACGGCACCACCACTCGCACCCCCATGGATGATGCCGATCCTCCAGGCCCTGAGAACCTGTTT GTGAACTACCTGTCCCGCATCCATCGTGAGGAGGACTTCCAGTTCATCCTCAAGCGTATAGCCCG GCTGCTGTCCAACCCCCTGCTCCAGACCTACCTGCCTAACTCCACCAAGAAGATCCAGTTCCACC AGGAGCTGCTACTTCTCTTCTGGAAGCTCTGCGACTTCAACAAGAAATTCCTCTTCTTCGTGCTG AAGAGCAGCGACCGTCCTAGACATCCTTGTCCCCATCCTCTTCTTCCTCACGATGCCCGGGCCGA TCAGTCT ORF Start: ATG at 1                    ORF Stop: end of sequence SEQ ID NO: 94           414 aa         MW at 46487.9 kD NOV16g, MGSTDSKLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVREESPS CG54443-06 Protein Sequence NLATLCYKAVERLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWSTVPGAGRC GQGEEDDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSCEYIWEAGVGFAH SPQPNYIHDMNRMELLKLLLTCFSEAMYLPPAPESGSTNPWVQFFCSTENRHALPLFTSLLNTV CAYDPVGYCIPYNHLLFSDYREPLVEEAAQVLIVTLDHDSASSASPTVDGTTTGTANDDADPPG PENIFVNYLSRIHREEDFQFILKGIARLLSNPLLQTYLPNSTKKIQFHQELLVLFWKLCDFNKK FLFFVLKSSDVLDILVPILFFLNDARADQS

[0430] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 16B. TABLE 16B Comparison of NOV16a against NOV16b through NOV16g. Identities/ Similarities for Protein NOV16a Residues/ the Matched Sequence Match Residues Region NOV16b 258 . . . 414  155/157 (98%) 30 . . . 186  155/157 (98%) NOV16c 1 . . . 414 388/414 (93%) 1 . . . 390 389/414 (93%) NOV16d 1 . . . 414 411/414 (99%) 1 . . . 414 412/414 (99%) NOV16e 1 . . . 414  414/414 (100%) 1 . . . 414  414/414 (100%) NOV16f 1 . . . 414  414/414 (100%) 1 . . . 414  414/414 (100%) NOV16g 1 . . . 414  414/414 (100%) 1 . . . 414  414/414 (100%)

[0431] Further analysis of the NOV16a protein yielded the following properties shown in Table 16C. TABLE 16C Protein Sequence Properties NOV16a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 11; pos. chg 2; neg. chg 1 H-region: length 0; peak value −0.21 PSG score: −4.61 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −5.12 possible cleavage site: between 48 and 49 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 3.13 (at 93) ALOM score: −1.28 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 2.33 Hyd Moment(95): 1.80 G content: 1 D/E content: 2 S/T content: 6 Score: −5.83 Gavel: indication of cleavage sites for mitochondrial preseq R-2 motif at 21 FRK|AV NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 7.7% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: MGSTDSK Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 43.5%: cytoplasmic 30.4%: mitochondrial 21.7%: nuclear  4.3%: peroxisomal >> indication for CG54443-03 is cyt (k = 23)

[0432] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16D. TABLE 16D Geneseq Results for NOV16a Identities/ Similarities for Geneseq Protein/Organism/Length NOV16a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value ABG70273 Human CG8841-like protein #2 - 1 . . . 414 411/414 (99%) 0.0 Homo sapiens, 788 aa. 1 . . . 414 412/414 (99%) [WO200255702-A2, 18 JUL. 2002] AAM79253 Human protein SEQ ID NO 1915 - 1 . . . 414 412/414 (99%) 0.0 Homo sapiens, 787 aa. 1 . . . 413 413/414 (99%) [WO200157190-A2, 09 AUG. 2001] ABG70272 Human CG8841-like protein #1 - 1 . . . 414 388/414 (93%) 0.0 Homo sapiens, 764 aa. 1 . . . 390 389/414 (93%) [WO200255702-A2, 18 JUL. 2002] ABB12112 Human secreted protein homologue, 1 . . . 271 259/272 (95%) e−151 SEQ ID NO: 2482 - Homo sapiens, 284 12 . . . 283  261/272 (95%) aa. [WO200157188-A2, 09 AUG. 2001] ABB64025 Drosophila melanogaster polypeptide 1 . . . 414 252/414 (60%) e−146 SEQ ID NO 18867 - Drosophila 1 . . . 398 310/414 (74%) melanogaster, 837 aa. [WO200171042-A2, 27 SEP. 2001]

[0433] In a BLAST search of public sequence databases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16E. TABLE 16E Public BLASTP Results for NOV16a Identities/ Protein Similarities for Accession NOV16a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value AAH35372 Hypothetical protein - Homo 1 . . . 414 413/414 (99%) 0.0 sapiens (Human), 788 aa. 1 . . . 414 414/414 (99%) Q8TE83 Hypothetical protein FLJ23821 - 1 . . . 414 413/414 (99%) 0.0 Homo sapiens (Human), 625 aa. 1 . . . 414 414/414 (99%) Q8R1F6 Hypothetical 88.8 kDa protein - 1 . . . 414 400/414 (96%) 0.0 Mus musculus (Mouse), 788 aa. 1 . . . 414 410/414 (98%) Q9NT34 Hypothetical protein - Homo 1 . . . 364 354/364 (97%) 0.0 sapiens (Human), 380 aa 1 . . . 363 355/364 (97%) (fragment). Q9V695 CG8841 protein - Drosophila 1 . . . 414 252/414 (60%) e−146 melanogaster (Fruit fly), 837 aa. 1 . . . 398 310/414 (74%)

Example 17

[0434] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A. TABLE 17A NOV17 Sequence Analyis SEQ ID NO: 95               752 bp NOV17a, CT CTGGCCCTCACCCTCATCTTGATCGCAGCCTCTGGTGCTGCGTGCGAAGTGAGGGACGTTTC CG58495-01 DNA Sequence TGTTGGAAGCCCTGGTATCCCCGGCACTCCTGGATCCCACGGCCTGCCAGGCAGGGACGGGAGA GATGGTGTCAAAGGAGACCCTGGCCCTCCAGGCGCCCCATGGTCCGCCTGGAGAAACACCTGTC CTCCTGGGAATAATGGGCTGCCTGGAGCCCCTGGTGTCCCTGGAGAGCGTGGAGAGAAGGGGGA GCCTGGCGAGAGAGGCCCTCCAGGGCTTCCAGCTCATCTAGATGAGGAGCTCCAAGCCACACTC CACGACTTCAGACATCAAATCCTGCAGACAACGGGAGCCCTCAGTCTGCAGGGCTCCATAATGA CAGTAGGAGAGAAGGTCTTCTCCAGCAATGGGCAGTCCATCACTTTTCATGCCATTCAGGAGGC ATGTGCCAGAGCAGGCGGCCGCATTGCTGTCCCAAGGAATCCAGAGGAAAATGAGGCCATTGCA AGCTTCGTGAAGAAGTACAACACATATGCCTATGTAGGCCTGACTGAGGGTCCCAGCCCTGGAG ACTTCCGCTACTCAGATGGGACCCCTGTAAACTACACCAACTGGTACCGAGGGGAGCCTGCAGG TCGGGGAAAAGAGAAGTGTGTGGAGATGTACACAGATGGGCAGTGGAATGACAGGAACTGCCTG TACTCCCGACTGACCATCTGTGAGTTCTGA GAGGCATTTAGGCCATGG ORF Start: at 3                            ORF Stop: TGA at 732 SEQ ID NO: 96               243 aa         MW at 25592.3 kD NOV17a, LALTLILMAASGAACEVRDVCVGSPGIPGTPGSTGLPGRDGRDGVKGDPGPPGPMGPPGETPCP CG58495-01 Protein Sequence PGNNGLPGAPGVPGERGEKGEPGERGPPGLPAHLDEELQATLHDFRHQILQTRGALSLQGSIMT VGEKVFSSNGQSITFDAIQEACARAGGRIAVPRNPEENEAIASFVKKYNTYAYVGLTEGPSPGD FRYSDGTPVNYTNWYRGEPAGRGKEKCVEMYTDCQWNDRNCLYSRLTICEF SEQ ID NO: 97               681 bp NOV17b, CCAAGCACCTGGAGGCTCTGTGTGTGGGTCGCTGATTTCTTGGAGCCTGAAAAGAAGGAGCAGC CG58495-03 DNA Sequence GACTGGACCCAGAGCC ATGTGGCTGTGCCCTCTGGCCCTCACCCTCATCTTGATGGCAGCCTCT GGTGCTGCGTGCGAAGTGAAGGAGCTCCAAGCCACACTCCACGACTTCAGACATCAAATCCTGC AGACAAGGGGAGCCCTCAGTCTGCAGGGCTCCATAATGACAGTAGGAGAGAAGGTCTTCTCTAG CAATGGGCAGTCCATCACTTTTGATGCCATTCAGGAGGCATGTGCCAGAGCAGGCGGCCGCATT GCTGTCCCAAGGAATCCAGAGGAAAATGAGGCCATTGCAAGCTTCGTGAAGAAGTACAACACAT ATGCCTATGTAGGCCTGACTGAGGGTCCCAGCCCTGGAGACTTCCGCTACTCAGATGGGACCCC TGTAAACTACACCAACTGGTACCGAGGGGAGCCTGCAGGTCGGGGAAAAGAGAAGTGTGTGGAG ATGTACAAGATGGGCAGTGGAATGACAGGAACTGCCCTGTACTCCCGACTGACCATCTGTGAGT TCTGA GAGGCATTTAGGCCATGGGACAGGGAGGATCCTGTCTGGCCTTCAGTTTCCATCCCCAG GATCCACTTGGTCTGTGAGATGCTAGAACTCCCTTTCAACA ORF Start: ATG at 81                       ORF Stop: TGA at 579 SEQ ID NO: 98               166 aa         MW at 18388.6 kD NOV17b, MWLCPLALTLILMAASGAACEVKELQATLHDFRHQILQTRGALSLQGSIMTVGKVFSSNGQSI CG58495-03 Protein Sequence TFDAIQEACARAGGRIAVPRNPEENEAIASFVKKYNTYAYVGLTEGSPGDFRYSDGTPVNYTN WYRGEPAGRGKEKCVEMYTDGQWNDRNCLYSRLTICEF SEQ ID NO: 99              1161 bp NOV17c, GGCTCTTTCTAGCTATAAACACTGCTTGCCGCGCTGCACTCCACCACGCCTCCTCCAAGTCCCA CG58495-02 DNA Sequence GCGAACCCGCGTGCAACCTGTCCCGACTCTAGCCGCCTCTTCAGCTCACGGATCAATTCCCAAG TCGCTGGAGGCTCTGTGTGTGGGAGCAGCGACTGGACCCAGAGCC ATGTGGCTGTGCCCTCTGG CCCTCAACCTCATCTTGATGGCAGCCTCTGGTGCTGTGTGCGAAGTGAAGGACGTTTGTGTTGG AAGCCCTGGTATCCCCGGCACTCCTGGATCCCACGGCCTGCCAGGCAGGGACGGGAGAGATGGT GTCAAAGGAGACCCTGGCCCTCCAGGCCCCATGGGTCCACCTGGAGAAATGCCATGTCCTCCTG GAAATGATGGGCTGCCTGGAGCCCCTGGTATCCCTGGAGAGTGTGGAGAGAAGGGGGAGCCTGG CGAGAGGGGCCCTCCAGGGCTTCCAGCTCATCTAGATGAGGAGCTCCAAGCCACACTCCACGAC TTTAGACATCAAATCCTGCAGACAAGGGGAGCCCTCAGTCTGCAGGGCTCCATAATGACAGTAG GAGAGAAGGTCTTCTCCAGCAATGGGCAGTCCATCACTTTTGATGCCATTCAGGAGGCATGTGC CAGAGCAGGCGGCCGCATTGCTGTCCCAAGGAATCCAGAGGAAAATGAGGCCATTGCAAGCTTC GTGAAGAAGTACAACACATAGCCTATGTAGGCCTGACTGAGGGTCCCAGCCCCTGGAGACTTCC GCTACTCAGACGGGACCCCTGTAAACTACACCAACTGGTACCGAGGGGAGCCCGCAGGTCGGGG AAAAGAGCAGTGTGTGGAGATGTACACAGATGGGCAGTGGAATGACAGGAACTGCCTGTACTCC CGACTGACCATCTGTGAGTTCTGA GAGGCATTTAGGCCATGGGACAGGGAGGACGCTCTCTGGC CTCCATCCTGAGGCTCCACTTGGTCTGTGAGATGCTAGAACTCCCTTCAACAGAATTGATCCCT GCTGCCCGTGCTGGAGAGCTTCAAGGTCAGCTTCCTGAGCGCTCTCTCGAGGAGTACACTAAGA AGCTCAACACCCAGTGAGGCGCCCGCCGCCGCCCCCCTTCCCGGTGCTCAGAATAAACGTTTCC AAAGTGGGA ORF Start: ATG at 174                      ORF Stop: TGA at 918 SEQ ID NO: 100              248 aa         MW at 26228.2 kD NOV17c, MWLCPLALNLILMAASGAVCEVKDVCVGSPGIPGTPGSHGLPGRDGRDGVKGDPGPPGPMGPPG CG58495-02 Protein Sequence EMPCPPGNDGLPGAPGIPGECGEKGEPGERGPPGLPAHLDEELQATLHDFRHQTLQTRGALSLQ GSIMTVGEKVFSSNGQSITFDAIQEACARAGGRIAVPRNPEENEAIASFVKKYNTYAYVGLTEG PSPGDFRYSDGTPVNYTNWYRGEPAGRGKEQCVEMYTDQQWNDRNCLYSRLTICEF

[0435] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B. TABLE 17B Comparison of NOV17a against NOV17b and NOV17c. Identities/ Similarities for Protein NOV17a Residues/ the Matched Sequence Match Residues Region NOV17b 100 . . . 243  143/144 (99%) 23 . . . 166  144/144 (99%) NOV17c 1 . . . 243 235/243 (96%) 6 . . . 248 239/243 (97%)

[0436] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C. TABLE 17C Protein Sequence Properties NOV17a SignalP Cleavage site between residues 16 and 17 analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 0; pos. chg 0; neg. chg 0 H-region: length 15; peak value 10.71 PSG score: 6.31 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): 2.44 possible cleavage site: between 15 and 16 >>> Seems to have a cleavable signal peptide (1 to 15) ALOM: Klein et al's method for TM region allocation Init position for calculation: 16 Tentative number of TMS(s) for the threshold 0.5: 0 Number of TMS(s) . . . fixed PERIPHERAL Likelihood = 7.37 (at 113) ALOM score: 7.37 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 7 Charge difference: −2.0 C(−1.0)-N(1.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 2.24 Hyd Moment(95): 0.60 G content: 1 D/E content: 1 S/T content: 2 Score: −6.05 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 9.1% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Indication: nuclear Reliability: 55.5 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 66.7%: extracellular, including cell wall 22.2%: nuclear 11.1%: mitochondrial >> indication for CG58495-01 is exc (k = 9)

[0437] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D. TABLE 17D Geneseq Results for NOV17a Identities/ Similarities for Geneseq Protein/Organism/Length NOV17a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value AAU76468 Human lung surfactant protein A - 1 . . . 243 241/243 (99%) e−147 Homo sapiens, 248 aa. 6 . . . 248 243/243 (99%) [WO200206301-A2, 24 JAN. 2002] AAY77989 Human SP-A amino acid sequence - 1 . . . 243 241/243 (99%) e−147 Homo sapiens, 248 aa. 6 . . . 248 243/243 (99%) [WO200011161-A1, 02 MAR. 2000] AAP70662 35 kd pulmonary surfactant protein - 1 . . . 243 240/243 (98%) e−146 Homo sapiens, 248 aa. 6 . . . 248 242/243 (98%) [WO8702037-A, 09 APR. 1987] AAR05091 Vector PSP 35K-1A-10 gene product 1 . . . 243 239/243 (98%) e−146 encoding pulmonary surfactant protein - 6 . . . 248 242/243 (99%) Homo sapiens, 248 aa. [US4882422-A, 21 NOV. 1989] AAB58135 Lung cancer associated polypeptide 1 . . . 243 238/243 (97%) e−145 sequence SEQ ID 473 - Homo sapiens, 17 . . . 259  239/243 (97%) 259 aa. [WO200055180-A2, 21 SEP. 2000]

[0438] In a BLAST search of public sequence databases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E. TABLE 17E Public BLASTP Results for NOV17a Identities/ Protein Similarities for Accession NOV17a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Region Value LNHUP1 pulmonary surfactant protein A precursor 1 . . . 243 240/243 (98%) e−146 (clone 1A) - human, 248 aa. 6 . . . 248 243/243 (99%) I51921 pulmonary surfactant-associated protein 1 . . . 243 238/243 (97%) e−145 A1 - human, 248 aa. 6 . . . 248 241/243 (98%) P07714 Pulmonary surfactant-associated protein 1 . . . 243 235/243 (96%) e−143 A precursor (SP-A) (PSP-A) (PSAP) 6 . . . 248 240/243 (98%) (Alveolar proteinosis protein) (35 kDa pulmonary surfactant-associated protein) - Homo sapiens (Human), 248 aa. LNHUPS pulmonary surfactant protein A precursor 1 . . . 243 232/243 (95%) e−141 (genomic clone) - human, 248 aa. 6 . . . 248 237/243 (97%) Q9TT06 Pulmonary surfactant protein A 1 . . . 243 183/243 (75%) e−114 (Pulmonary surfactant-associated protein 6 . . . 248 208/243 (85%) A) - Ovis aries (Sheep), 248 aa.

[0439] PFam analysis indicates that the NOV17a protein contains the domains shown in the Table 17F. TABLE 17F Domain Analysis of NOV17a Identities/ NOV17a Similarities for Pfam Match the Matched Expect Domain Region Region Value Collagen 32 . . . 92 34/61 (56%) 0.00019 49/61 (80%) Xlink 131 . . . 158 13/32 (41%) 0.41 19/32 (59%) lectin_c 139 . . . 243 48/125 (38%)  5e−45 92/125 (74%) 

Example 18

[0440] The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A. TABLE 18A NOV18 Sequence Analysis SEQ ID NO: 101 349 b NOV18a, GGTGAGACAAGGAAGAGG ATGTCTGAGCTGGAGAAGGCCATGGTGGCCCTCATCGACGTTTTCC CG97482-01 DNA Sequence ACCAATATTCTGGAAGGGAGGGAGACAAGCACAAGCTGAAGAAATCCGAACTCAACGAGCTCAT CAACAATGAGCTTTCCCATTTCTTAGAGGAAATCAAAGAGCAGGAGGTTGTGGACAAAGTCATG GAAACACTGGACAATGATGGAGACGGCGAATGTGACTTCCACGAATTCATGGCCTTTGTTGCCA TGGTTACTACTGCCCGCCACGAGTTCTTTGAACATGAGTGA GATTAGAAAGCAGCCAAACCTTT CCTGTAACAGAGACGGTCATGCAAGAAAG ORF Start: ATG at 19 ORF Stop: TGA at 295 SEQ ID NO: 102  92 aa MW at 10766.0kD NOV18a, MSELEKAMVALIDVFHQYSGREGDKHKLKKSELKELINNELSHFLEEIKEQEVVDKVMETLDND CG97482-01 Protein Sequence GDGECDFQEFMAFVAMVTTARHEFFEHE SEQ ID NO: 103 271 bp GGTGAGACAAGGAAGAGG ATGTCTGAGCTGGAGAAGGCCATGGTGGCCCTCATCGACGTTTTCC NOV18b, ACCAATATTCTGGAAGGGAGGGAGACAAGCACAAGCTGAAGAAATCCGAACTCAAGGAGCTCAT CG97482-02 DNA Sequence CAACAATGAGCTTTCCCATTTCTTAGAGGAAATCAAAGAGCACGAGGTTGTGGTTACTACTGCC TGCCACGAGTTCTTTGAACATGAGTGA GATTAGAAAGCAGCCAAACCTTTCCTGTAACAGAGAC GGTCATGCAAGAAAG ORF Start: ATG at 19 ORE Stop: TGA at 217 SEQ ID NO: 104  66 aa MW at 7772.7 kD NOV18b, MSELEKAMVALIDVFHQYSGREGDKHKLKKSELKELINNELSHFLEEIKEQEVVVTTACHEFFE CG97482-02 Protein Sequence HE

[0441] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B. TABLE 18B Comparison of NOV18a against NOV18b. Identities/ Similarities for Protein NOV1a Residues/ the Matched Sequence Match Residues Region NOV18b 1 . . . 92 65/92 (70%) 1 . . . 66 65/92 (70%)

[0442] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C. TABLE 18C Protein Sequence Properties NOV18a SignalP No Known Signal Sequence Indicated analysis: PSORT II PSG: a new signal peptide prediction method analysis: N-region: length 6; pos. chg 1; neg. chg 2 H-region: length 6; peak value 0.00 PSG score: −4.40 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: −2.1): −8.88 possible cleavage site: between 20 and 21 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 0 Number of TMS(s) . . . fixed PERIPHERAL Likelihood = 7.32 (at 68) ALOM score: 7.32 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 2.53 Hyd Moment(95): 2.95 G content: 0 D/E content: 2 S/T content: 1 Score: −7.61 Gavel: indication of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.9% NLS Score: −0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: none RNA-binding motif: none Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern: none Prenylation motif: none memYQRL: transport motif from cell surface to Golgi: none Tyrosines in the tail: none Dileucine motif in the tail: none checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none discrimination Indication: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 56.5%: cytoplasmic 30.4%: nuclear  8.7%: mitochondrial  4.3%: Golgi >> indication for CG97482-01 is cyt (k = 23)

[0443] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18D. TABLE 18D Geneseq Results for NOV18a Identities/ Similarities for Geneseq Protein/Organism/Length NOV1a Residues/ the Matched Expect Identifier [Patent #, Date] Match Residues Region Value ABB97495 Novel human protein SEQ ID NO: 763 - 1 . . . 92 91/92 (98%) 3e−47 Homo sapiens, 92 aa. 1 . . . 92 91/92 (98%) [WO200222660-A2, 21 MAR. 2002] ABP51390 Human MDDT SEQ ID NO 412 - 1 . . . 92 89/92 (96%) 3e−6  Homo sapiens, 97 aa. 6 . . . 97 90/92 (97%) [WO200240715-A2, 23 MAY 2002] AAW46607 Human brain protein S100b beta 2 . . . 92 84/91 (92%) 4e−43 subunit - Homo sapiens, 91 aa. 1 . . . 91 87/91 (95%) [WO9801471-A1, 15 JAN. 1998] AAM40258 Human polypeptide SEQ ID NO 3403 - 2 . . . 89 52/88 (59%) 2e−23 Homo sapiens, 94 aa. 3 . . . 90 66/88 (74%) [WO200153312-A1, 26 JUL. 2001] AAB45531 Human S100A1 protein - Homo 2 . . . 89 52/88 (59%) 2e−23 sapiens, 94 aa. [DE19915485-A1, 3 . . . 90 66/88 (74%) 19 OCT. 2000]

[0444] In a BLAST search of public sequence databases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18E. TABLE 18E Public BLASTP Results for NOV18a Identities/ Protein Similarities for Accession NOV1a Residues/ the Matched Expect Number Protein/Organism/Length Match Residues Portion Value CAD35011 Sequence 319 from Patent WO0222660 - 1 . . . 92 91/92 (98%) 7e−7  Homo sapiens (Human), 92 aa. 1 . . . 92 91/92 (98%) P04271 S-100 protein, beta chain - Homo 2 . . . 92 90/91 (98%) 3e−46 sapiens (Human), 91 aa. 1 . . . 91 90/91 (98%) A48015 S-100 protein beta chain - mouse, 92 aa. 1 . . . 92 90/92 (97%) 4e−6  1 . . . 92 90/92 (97%) A26557 S-100 protein beta chain - rat, 92 aa. 1 . . . 92 89/92 (96%) 8e−46 1 . . . 92 90/92 (97%) AAA72205 SYNTHETIC 1 . . . 92 88/92 (95%) 1e−45 CALCIUM-MODULATED PROTEIN 1 . . . 92 91/92 (98%) S100-BETA GENE, 5′ END - synthetic construct, 92 aa (fragment).

[0445] PFam analysis indicates that the NOV1a protein contains the domains shown in the Table 18F. TABLE 18F Domain Analysis of NOV18a Identities/ NOV18a Similarities for Pfam Match the Matched Expect Domain Region Region Value S_100 4 . . . 47 28/44 (64%) 3.6e−23 41/44 (93%) efhand 53 . . . 81   9/29 (31%) 0.0012 25/29 (86%)

Example B Sequencing Methodology and Identification of NOVX Clones

[0446] 1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.

[0447] 2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0448] 3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.

[0449] The laboratory screening was performed using the methods summarized below: cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from E. coli into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).

[0450] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0451] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).

[0452] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the predicted sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.

[0453] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.

[0454] 6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.

[0455] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.

Example C Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0456] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM®) 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0457] RNA integrity from all samples is controlled for quality by visual assessment of agarose gel electropherograms using 28S and 18S ribosomal RNA staining intensity ratio as a guide (2:1 to 2.5:1 28s: 18s) and the absence of low molecular weight RNAs that would be indicative of degradation products. Samples are controlled against genomic DNA contamination by RTQ PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.

[0458] First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 ul) was converted to cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix Reagents (Applied Biosystems; Catalog No. 4309169) and gene-specific primers according to the manufacturer's instructions.

[0459] In other cases, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation; Catalog No. 18064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 μg of total RNA were performed in a volume of 20 μl and incubated for 60 minutes at 42° C. This reaction can be scaled up to 50 μg of total RNA in a final volume of 100 μl. sscDNA samples are then normalized to reference nucleic acids as described previously, using 1× TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.

[0460] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers: primer concentration=250 nM, primer melting temperature (Tm) range=58°-60° C., primer optimal Tm=59° C., maximum primer difference=2° C., probe does not have 5′G, probe Tm must be 10° C. greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, Tex., USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5′ and 3′ ends of the probe, respectively. Their final concentrations were: forward and reverse primers, 900 nM each, and probe, 200 nM.

[0461] PCR conditions: When working with RNA samples, normalized RNA from each tissue and each cell line was spotted in each well of either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktails included either a single gene specific probe and primers set, or two multiplexed probe and primers sets (a set specific for the target clone and another gene-specific set multiplexed with the target probe). PCR reactions were set up using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer's instructions. Reverse transcription was performed at 48° C. for 30 minutes followed by amplification/PCR cycles as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100.

[0462] When working with sscDNA samples, normalized sscDNA was used as described previously for RNA samples. PCR reactions containing one or two sets of probe and primers were set up as described previously, using 1× TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions. PCR amplification was performed as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were analyzed and processed as described previously.

[0463] Panels 1, 1.1, 1.2, and 1.3D

[0464] The plates for Panels 1, 1.1, 1.2 and 1.3D include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in these panels are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in these panels are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on these panels are comprised of samples derived from all major organ systems from single adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose.

[0465] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0466] ca.=carcinoma,

[0467] *=established from metastasis,

[0468] met=metastasis,

[0469] s cell var=small cell variant,

[0470] non-s=non-sm=non-small,

[0471] squam=squamous,

[0472] pl. eff=pl effusion=pleural effusion,

[0473] glio=glioma,

[0474] astro=astrocytoma, and

[0475] neuro=neuroblastoma.

[0476] General_screening_panel_v1.4, v1.5, v1.6 and 1.7

[0477] The plates for Panels 1.4, 1.5, 1.6 and 1.7 include 2 control wells (genomic DNA control and chemistry control) and 88 to 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, 1.6 and 1.7 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, 1.5, 1.6 and 1.7 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, 1.5, 1.6 and 1.7 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.

[0478] Panels 2D, 2.2, 2.3 and 2.4

[0479] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.

[0480] HASS Panel v 1.0

[0481] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, 81 of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, Md.) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.

[0482] ARDAIS Panel v 1.0

[0483] The plates for ARDAIS panel v 1.0 generally include 2 control wells and 22 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Corporation. The tissues are derived from human lung malignancies (lung adenocarcinoma or lung squamous cell carcinoma) and in cases where indicated many malignant samples have “matched margins” obtained from noncancerous lung tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue) in the results below. The tumor tissue and the “matched margins” are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). Unmatched malignant and non-malignant RNA samples from lungs were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state of the patient.

[0484] Panel 3D, 3.1 and 3.2

[0485] The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1., 1.2, 1.3D, 1.4, 1.5, and 1.6 are of the most common cell lines used in the scientific literature.

[0486] Panels 4D, 4R, and 4.1D

[0487] Panel 4 includes samples on a 96 well plate (2 control wells, 94 test samples) composed of RNA (Panel 4R) or cDNA (Panels 4D/4.1D) isolated from various human cell lines or tissues related to inflammatory conditions. Total RNA from control normal tissues such as colon and lung (Stratagene, La Jolla, Calif.) and thymus and kidney (Clontech) was employed. Total RNA from liver tissue from cirrhosis patients and kidney from lupus patients was obtained from BioChain (Biochain Institute, Inc., Hayward, Calif.). Intestinal tissue for RNA preparation from patients diagnosed as having Crohn's disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, Pa.).

[0488] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, Md.) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.

[0489] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×10⁶ cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10⁻⁵M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.

[0490] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 110 μg/ml for 6 and 12-14 hours.

[0491] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer's instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) and plated at 10⁶ cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.

[0492] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 10⁶ cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24, 48 and 72 hours.

[0493] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 10⁵-10⁶ cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 M non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.

[0494] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×10⁵ cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×10⁵ cells/m. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10⁻⁵M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0495] For these cell lines and blood cells, RNA was prepared by lysing approximately 10⁷ cells/ml using Trizol (Gibco BRL). Briefly, 1/10 volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 51 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.

[0496] AI_Comprehensive Panel_v1.0

[0497] The plates for AI_comprehensive panel_v1.0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, Md.). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.

[0498] Joint tissues including synovial fluid, synovium, bone and cartilage were obtained from patients undergoing total knee or hip replacement surgery at the Backus Hospital. Tissue samples were immediately snap frozen in liquid nitrogen to ensure that isolated RNA was of optimal quality and not degraded. Additional samples of osteoarthritis and rheumatoid arthritis joint tissues were obtained from Clinomics. Normal control tissues were supplied by Clinomics and were obtained during autopsy of trauma victims.

[0499] Surgical specimens of psoriatic tissues and adjacent matched tissues were provided as total RNA by Clinomics. Two male and two female patients were selected between the ages of 25 and 47. None of the patients were taking prescription drugs at the time samples were isolated.

[0500] Surgical specimens of diseased colon from patients with ulcerative colitis and Crohns disease and adjacent matched tissues were obtained from Clinomics. Bowel tissue from three female and three male Crohn's patients between the ages of 41-69 were used. Two patients were not on prescription medication while the others were taking dexamethasone, phenobarbital, or tylenol. Ulcerative colitis tissue was from three male and four female patients. Four of the patients were taking lebvid and two were on phenobarbital.

[0501] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-lanti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.

[0502] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0503] AI=Autoimmunity

[0504] Syn=Synovial

[0505] Normal=No apparent disease

[0506] Rep22/Rep20=individual patients

[0507] RA=Rheumatoid arthritis

[0508] Backus=From Backus Hospital

[0509] OA=Osteoarthritis

[0510] (SS) (BA) (MF)=Individual patients

[0511] Adj=Adjacent tissue

[0512] Match control=adjacent tissues

[0513] -M=Male

[0514] -F=Female

[0515] COPD=Chronic obstructive pulmonary disease

[0516] AI.05 Chondrosarcoma

[0517] The AI.05 chondrosarcoma plates are comprised of SW1353 cells that had been subjected to serum starvation and treatment with cytokines that are known to induce MMP (1, 3 and 13) synthesis (eg. IL1beta). These treatments include: IL-1beta (10 ng/ml), IL-1beta+TNF-alpha (50 ng/ml), IL-1beta+Oncostatin (50 ng/ml) and PMA (100 ng/ml). The SW1353 cells were obtained from the ATCC (American Type Culture Collection) and were all cultured under standard recommended conditions. The SW1353 cells were plated at 3×10⁵ cells/ml (in DMEM medium-10% FBS) in 6-well plates. The treatment was done in triplicate, for 6 and 18 h. The supernatants were collected for analysis of MMP 1, 3 and 13 production and for RNA extraction. RNA was prepared from these samples using the standard procedures.

[0518] Panels 5D and 5I

[0519] The plates for Panel 5D and 5I include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were also obtained.

[0520] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (<1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:

[0521] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0522] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0523] Patient 10: Diabetic Hispanic, overweight, on insulin

[0524] Patient 11: Nondiabetic African American and overweight

[0525] Patient 12: Diabetic Hispanic on insulin

[0526] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:

[0527] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0528] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0529] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0530] Human cell lines were generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells, and adrenal cortical adenoma cells. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. All samples were processed at CuraGen to produce single stranded cDNA.

[0531] Panel 5I contains all samples previously described with the addition of pancreatic islets from a 58 year old female patient obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at an outside source and delivered to CuraGen for addition to panel 5I.

[0532] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0533] GO Adipose=Greater Omentum Adipose

[0534] SK=Skeletal Muscle

[0535] UT=Uterus

[0536] PL=Placenta

[0537] AD=Adipose Differentiated

[0538] AM=Adipose Midway Differentiated

[0539] U=Undifferentiated Stem Cells

[0540] Panel CNSD.01

[0541] The plates for Panel CNSD.01 include two control wells and 94 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center. Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.

[0542] Disease diagnoses are taken from patient records. The panel contains two brains from each of the following diagnoses: Alzheimer's disease, Parkinson's disease, Huntington's disease, Progressive Supernuclear Palsy, Depression, and “Normal controls”. Within each of these brains, the following regions are represented: cingulate gyrus, temporal pole, globus palladus, substantia nigra, Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17 (occipital cortex). Not all brain regions are represented in all cases; e.g., Huntington's disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington's cases. Likewise Parkinson's disease is characterized by degeneration of the substantia nigra making this region more difficult to obtain. Normal control brains were examined for neuropathology and found to be free of any pathology consistent with neurodegeneration.

[0543] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0544] PSP=Progressive supranuclear palsy

[0545] Sub Nigra=Substantia nigra

[0546] Glob Palladus=Globus palladus

[0547] Temp Pole=Temporal pole

[0548] Cing Gyr=Cingulate gyrus

[0549] BA 4=Brodman Area 4

[0550] Panel CNS_Neurodegeneration_V1.0

[0551] The plates for Panel CNS_Neurodegeneration_V1.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.

[0552] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer's disease (AD) patients, and eight brains from “Normal controls” who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer's like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer's like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages of the disease; the occipital cortex is spared in AD and therefore acts as a “control” region within AD patients. Not all brain regions are represented in all cases.

[0553] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0554] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0555] Control=Control brains; patient not demented, showing no neuropathology

[0556] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0557] SupTemporal Ctx=Superior Temporal Cortex

[0558] Inf Temporal Ctx=Inferior Temporal Cortex

[0559] A. CG115907-02 (NOV2d), CG115907-03 (NOV2c), and CG115907-04 (NOV2b): PK-120.

[0560] Expression of gene CG115907-02, CG115907-03, and CG115907-04 was assessed using the primer-probe sets Ag6155, Ag6156 and Ag6131, described in Tables AA, AB and AC. Results of the RTQ-PCR runs are shown in Tables AD and AE. Please note that primer-probe set Ag6155 is specific for CG115907-03 and Ag6156 is specific for CG115907-04. TABLE AA Probe Name Ag6155 Start SEQ ID Primers Sequeces Length Position No Forward 5′-atcttgcctgcttcagcaa-3′ 119 2113 105 Probe TET-5′-caaatcctgatccagctgtgtctcgt-3′-TAMRA 26 2144 106 Reverse 5′-ggatggcagacatattcatgac-3′ 22 2170 107

[0561] TABLE AR Probe Name Ag6156 Start SEQ ID Primers Sequnces Length Position No Forward 5′-ggccatcttgcctgctt-3′ 17 2109 108 Probe TET-5′-atcctgatccagctgtgtctcgtgtc-3′-TAMRA 26 2147 109 Reverse 5′-ctccctctcatactgcatattcat-3′ 24 2173 110

[0562] TABLE AC Probe Name Ag6131 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gtccactcagctggagctg-3′ 119 1981 111 Probe TET-5′-aacttggactcccaggacctcctgat-3′-TAMRA 26 2045 112 Reverse 5′-cagctggatcaggatttgag-3′ 20 2142 113

[0563] TABLE AD CNS neurodegeneration v1.0 Rel. Exp. (%) Ag6131, Run Tissue Name 253574594 AD 1 Hippo 0.0 AD 2 Hippo 25.0 AD 3 Hippo 0.0 AD 4 Hippo 11.7 AD 5 Hippo 99.3 AD 6 Hippo 55.1 Control 2 Hippo 37.6 Control 4 Hippo 14.3 Control (Path) 3 Hippo 9.0 AD 1 Temporal Ctx 2.6 AD 2 Temporal Ctx 0.0 AD 3 Temporal Ctx 0.0 AD 4 Temporal Ctx 22.1 AD 5 Inf Temporal Ctx 100.0 AD 5 Sup Temporal Ctx 28.9 AD 6 Inf Temporal Ctx 56.6 AD 6 Sup Temporal Ctx 39.2 Control 1 Temporal Ctx 0.0 Control 2 Temporal Ctx 33.0 Control 3 Temporal Ctx 19.9 Control 3 Temporal Ctx 9.0 Control (Path) 1 Temporal Ctx 57.0 Control (Path) 2 Temporal Ctx 55.5 Control (Path) 3 Temporal Ctx 3.4 Control (Path) 4 Temporal Ctx 51.8 AD 1 Occipital Ctx 3.8 AD 2 Occipital Ctx (Missing) 0.0 AD 3 Occipital Ctx 0.0 AD 4 Occipital Ctx 10.6 AD 5 Occipital Ctx 22.8 AD 6 Occipital Ctx 29.7 Control 1 Occipital Ctx 0.0 Control 2 Occipital Ctx 79.6 Control 3 Occipital Ctx 30.8 Control 4 Occipital Ctx 9.0 Control (Path) 1 Occipital Ctx 68.8 Control (Path) 2 Occipital Ctx 17.7 Control (Path) 3 Occipital Ctx 5.0 Control (Path) 4 Occipital Ctx 20.6 Control 1 Parietal Ctx 0.0 Control 2 Parietal Ctx 59.0 Control 3 Parietal Ctx 11.1 Control (Path) 1 Parietal Ctx 26.4 Control (Path) 2 Parietal Ctx 13.5 Control (Path) 3 Parietal Ctx 4.1 Control (Path) 4 Parietal Ctx 56.3

[0564] TABLE AE General screening panel v1.5 Rel. Exp. (%) Ag6131, Run Tissue Name 253101092 Adipose 0.0 Melanoma* Hs688(A).T 0.0 Melanoma* Hs688(B).T 0.0 Melanoma* M14 0.1 Melanoma* LOXIMVI 0.0 Melanoma* SK-MEL-5 0.0 Squamous cell carcinoma SCC-4 0.0 Testis Pool 0.1 Prostate ca.* (bone met) PC-3 0.0 Prostate Pool 0.0 Placenta 0.0 Uterus Pool 0.0 Ovarian ca. OVCAR-3 0.0 Ovarian ca. SK-OV-3 0.1 Ovarian ca. OVCAR-4 0.0 Ovarian ca. OVCAR-5 0.0 Ovarian ca. IGROV-1 0.0 Ovarian ca. OVCAR-8 0.0 Ovary 1.3 Breast ca. MCF-7 0.0 Breast ca. MDA-MB-231 0.1 Breast ca. BT 549 0.1 Breast ca. T47D 0.0 Breast ca. MDA-N 0.0 Breast Pool 0.2 Trachea 0.2 Lung 0.2 Fetal Lung 0.8 Lung ca. NCI-N417 0.0 Lung ca. LX-1 0.1 Lung ca. NCI-H146 0.0 Lung ca. SHP-77 0.0 Lung ca. A549 0.2 Lung ca. NCI-H526 0.0 Lung ca. NCI-H23 0.1 Lung ca. NCI-H460 0.0 Lung ca. HOP-62 0.0 Lung ca. NCI-H522 0.1 Liver 100.0 Fetal Liver 41.2 Liver ca. HepG2 0.0 Kidney Pool 0.7 Fetal Kidney 0.5 Renal ca. 786-0 0.0 Renal ca. A498 0.0 Renal ca. ACHN 0.0 Renal ca. UO-31 0.0 Renal ca. TK-10 0.1 Bladder 12.3 Gastric ca. (liver met.) NCI-N87 0.1 Gastric ca. KATO III 0.0 Colon ca. SW-948 0.0 Colon ca. SW480 0.0 Colon ca.* (SW480 met) SW620 0.0 Colon ca. HT29 0.0 Colon ca. HCT-116 0.0 Colon ca. CaCo-2 0.2 Colon cancer tissue 0.1 Colon ca. SW1116 0.0 Colon ca. Colo-205 0.0 Colon ca. SW-48 0.0 Colon Pool 0.1 Small Intestine Pool 0.1 Stomach Pool 0.1 Bone Marrow Pool 0.1 Fetal Heart 0.0 Heart Pool 0.2 Lymph Node Pool 0.2 Fetal Skeletal Muscle 2.0 Skeletal Muscle Pool 1.7 Spleen Pool 0.1 Thymus Pool 0.4 CNS cancer (glio/astro) U87-MG 0.0 CNS cancer (glio/astro) U-118-MG 0.0 CNS cancer (neuro; met) SK-N-AS 0.0 CNS cancer (astro) SF-539 0.0 CNS cancer (astro) SNB-75 0.1 CNS cancer (glio) SNB-19 0.0 CNS cancer (glio) SF-295 1.0 Brain (Amygdala) Pool 0.1 Brain (cerebellum) 0.4 Brain (fetal) 0.2 Brain (Hippocampus) Pool 0.1 Cerebral Cortex Pool 0.0 Brain (Substantia nigra) Pool 0.3 Brain (Thalamus) Pool 0.2 Brain (whole) 3.6 Spinal Cord Pool 0.1 Adrenal Gland 0.6 Pituitary gland Pool 0.0 Salivary Gland 0.0 Thyroid (female) 0.0 Pancreatic ca. CAPAN2 0.0 Pancreas Pool 2.3

[0565] CNS_neurodegeneration_v1.0 Summary: Ag6131 Low levels of expression of this gene is detected in the brains from control and Alzheimer's patients. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0566] Ag6155/Ag6156 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0567] General_screening_panel_v1.5 Summary: Ag6131 Highest expression of this gene is detected in liver (CT=25.2). High expression of this gene is mainly seen in adult and fetal liver, with moderate to low levels of expression in adult and fetal skeletal muscle, adernal gland and pancrease. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0568] In addition, moderate to low expression of this gene is also seen in whole brain, fetal brain, substantia nigra, thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0569] Low expression of this gene is also seen in a brain cancer SF-295 cell line. Therefore, therapeutic modulation of this gene may be useful in the treatment of brain cancer.

[0570] Ag6155/Ag6156 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0571] Ag6155/Ag6156 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0572] B. CG139008-01 (NOV3a): Novel Secreted.

[0573] Expression of gene CG139008-01 was assessed using the primer-probe sets Ag243 and Ag7477, described in Tables BA and BB. Results of the RTQ-PCR runs are shown in Tables BC and BD. TABLE BA Probe Name Ag243 Start SEQ ID Primers Sequnces Length Position No Forward 5′-caagggcatcaccaatttga-3′ 120 186 114 Probe TET-5′-aggatgtccagctgcccgtcatca-3′-TAMRA 24 212 115 Reverse 5′-gcccactccaggtacaaagttc-3′ 22 240 116

[0574] TABLE BB Probe Name Ag7477 Start SEQ ID Primers Sequnces Length Position No Forward 5′-ttctttggacagattactgagctt-3′ 124 1134 117 Probe TET-5′-tcctcatcgattggcaacttcaatga-3′-TAMRA 26 1168 118 Reverse 5′-tcttcgagatagctggtgatg-3′ 21 1212 119

[0575] TABLE BC Panel 1.3D Rel. Exp. (%) Ag243, Run Tissue Name 156536275 Liver adenocarcinoma 0.0 Pancreas 0.0 Pancreatic ca. CAPAN2 0.0 Adrenal gland 0.0 Thyroid 0.0 Salivary gland 17.6 Pituitary gland 0.0 Brain (fetal) 0.0 Brain (whole) 0.0 Brain (amygdala) 0.0 Brain (cerebellum) 0.0 Brain (hippocampus) 0.0 Brain (substantia nigra) 0.0 Brain (thalamus) 0.0 Cerebral Cortex 0.0 Spinal cord 0.0 glio/astro U87-MG 0.0 glio/astro U-118-MG 0.0 astrocytoma SW1783 0.0 neuro*; met SK-N-AS 0.0 astrocytoma SF-539 0.0 astrocytoma SNB-75 0.0 glioma SNB-19 0.0 glioma U251 0.0 glioma SF-295 0.0 Heart (fetal) 0.0 Heart 0.0 Skeletal muscle (fetal) 0.0 Skeletal muscle 0.0 Bone marrow 0.0 Thymus 0.0 Spleen 0.0 Lymph node 0.0 Colorectal 0.0 Stomach 0.0 Small intestine 0.0 Colon ca. SW480 0.0 Colon ca.* SW620(SW480 met) 0.0 Colon ca. HT29 0.0 Colon ca. HCT-116 0.0 Colon ca. CaCo-2 0.0 Colon ca. tissue(ODO3866) 0.0 Colon ca. HCC-2998 0.0 Gastric ca.* (liver met) NCI-N87 0.0 Bladder 0.0 Trachea 100.0 Kidney 0.0 Kidney (fetal) 0.0 Renal ca. 786-0 0.0 Renal ca. A498 0.0 Renal ca. RXF 393 0.0 Renal ca. ACHN 0.0 Renal ca. UO-31 0.0 Renal ca. TK-10 0.0 Liver 0.0 Liver (fetal) 0.0 Liver ca. (hepatoblast) HepG2 46.3 Lung 0.0 Lung (fetal) 0.0 Lung ca. (small cell) LX-1 0.0 Lung ca. (small cell) NCI-H69 0.0 Lung ca. (s. cell var.) SHP-77 0.0 Lung ca. (large cell)NCI-H460 0.0 Lung ca. (non-sm. cell) A549 0.0 Lung ca. (non-s. cell) NCI-H23 0.0 Lung ca. (non-s. cell) HOP-62 0.0 Lung ca. (non-s. cl) NCI-H522 0.0 Lung ca. (squam.) SW 900 0.0 Lung ca. (squam.) NCI-H596 0.0 Mammary gland 0.0 Breast ca.* (pl. ef) MCF-7 0.0 Breast ca.* (pl. ef) MDA-MB-231 0.0 Breast ca.* (pl. ef) T47D 0.0 Breast ca. BT-549 0.0 Breast ca. MDA-N 0.0 Ovary 0.0 Ovarian ca. OVCAR-3 0.0 Ovarian ca. OVCAR-4 0.0 Ovarian ca. OVCAR-5 0.0 Ovarian ca. OVCAR-8 0.0 Ovarian ca. IGROV-1 0.0 Ovarian ca.* (ascites) SK-OV-3 0.0 Uterus 0.0 Placenta 0.0 Prostate 0.0 Prostate ca.* (bone met)PC-3 0.0 Testis 0.0 Melanoma Hs688(A).T 0.0 Melanoma* (met) Hs688(B).T 0.0 Melanoma UACC-62 0.0 Melanoma M14 0.0 Melanoma LOX IMVI 0.0 Melanoma* (met) SK-MEL-5 0.0 Adipose 0.0

[0576] TABLE BD Panel 2D Rel. Exp. (%) Ag243, Run Tissue Name 156536477 Normal Colon 0.0 CC Well to Mod Diff (ODO3866) 0.0 CC Margin (ODO3866) 0.0 CC Gr.2 rectosigmoid (ODO3868) 0.0 CC Margin (ODO3868) 0.0 CC Mod Diff (ODO3920) 0.0 CC Margin (ODO3920) 0.0 CC Gr.2 ascend colon (ODO3921) 0.0 CC Margin (ODO3921) 0.0 CC from Partial Hepatectomy 0.0 (ODO4309) Mets Liver Margin (ODO4309) 0.0 Colon mets to lung (OD04451-01) 0.0 Lung Margin (OD04451-02) 0.0 Normal Prostate 6546-1 0.0 Prostate Cancer (OD04410) 21.9 Prostate Margin (OD04410) 0.0 Prostate Cancer (OD04720-01) 0.0 Prostate Margin (OD04720-02) 0.0 Normal Lung 061010 0.0 Lung Met to Muscle (ODO4286) 0.0 Muscle Margin (ODO4286) 0.0 Lung Malignant Cancer (OD03126) 15.8 Lung Margin (OD03126) 0.0 Lung Cancer (OD04404) 0.0 Lung Margin (OD04404) 0.0 Lung Cancer (OD04565) 0.0 Lung Margin (OD04565) 0.0 Lung Cancer (OD04237-01) 0.0 Lung Margin (OD04237-02) 0.0 Ocular Mel Met to Liver (ODO4310) 0.0 Liver Margin (ODO4310) 0.0 Melanoma Mets to Lung (OD04321) 0.0 Lung Margin (OD04321) 0.0 Normal Kidney 0.0 Kidney Ca, Nuclear grade 2 0.0 (OD04338) Kidney Margin (OD04338) 0.0 Kidney Ca Nuclear grade 1/2 0.0 (OD04339) Kidney Margin (OD04339) 0.0 Kidney Ca, Clear cell type (OD04340) 0.0 Kidney Margin (OD04340) 0.0 Kidney Ca, Nuclear grade 3 0.0 (OD04348) Kidney Margin (OD04348) 0.0 Kidney Cancer (OD04622-01) 0.0 Kidney Margin (OD04622-03) 0.0 Kidney Cancer (OD04450-01) 0.0 Kidney Margin (OD04450-03) 0.0 Kidney Cancer 8120607 0.0 Kidney Margin 8120608 0.0 Kidney Cancer 8120613 0.0 Kidney Margin 8120614 0.0 Kidney Cancer 9010320 0.0 Kidney Margin 9010321 0.0 Normal Uterus 0.0 Uterus Cancer 064011 0.0 Normal Thyroid 0.0 Thyroid Cancer 064010 0.0 Thyroid Cancer A302152 0.0 Thyroid Margin A302153 0.0 Normal Breast 0.0 Breast Cancer (OD04566) 0.0 Breast Cancer (OD04590-01) 0.0 Breast Cancer Mets 0.0 (OD04590-03) Breast Cancer Metastasis 0.0 (OD04655-05) Breast Cancer 064006 0.0 Breast Cancer 1024 0.0 Breast Cancer 9100266 100.0 Breast Margin 9100265 0.0 Breast Cancer A209073 0.0 Breast Margin A209073 0.0 Normal Liver 0.0 Liver Cancer 064003 0.0 Liver Cancer 1025 0.0 Liver Cancer 1026 21.9 Liver Cancer 6004-T 0.0 Liver Tissue 6004-N 0.0 Liver Cancer 6005-T 0.0 Liver Tissue 6005-N 0.0 Normal Bladder 0.0 Bladder Cancer 1023 0.0 Bladder Cancer A302173 0.0 Bladder Cancer (OD04718-01) 0.0 Bladder Normal Adjacent 0.0 (OD04718-03) Normal Ovary 0.0 Ovarian Cancer 064008 0.0 Ovarian Cancer (OD04768-07) 0.0 Ovary Margin (OD04768-08) 0.0 Normal Stomach 0.0 Gastric Cancer 9060358 0.0 Stomach Margin 9060359 0.0 Gastric Cancer 9060395 0.0 Stomach Margin 9060394 0.0 Gastric Cancer 9060397 0.0 Stomach Margin 9060396 0.0 Gastric Cancer 064005 0.0

[0577] Panel 1 Summary: Ag243 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0578] Panel 1.3D Summary: Ag243 Expression of this gene is restricted to the trachea and a liver cancer cell line (CTs=33.5-34.5). Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of liver cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of liver cancer.

[0579] Panel 2D Summary: Ag243 Expression of this gene is restricted to the a breast cancer cell line (CT=34.5). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast cancer.

[0580] Panel 4.1D Summary: Ag7477 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0581] Panel 4D Summary: Ag243 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0582] C. CG165528-01 (NOV9a): Neurexin I Alpha Precursor.

[0583] Expression of gene CG165528-01 was assessed using the primer-probe set Ag5964, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB and CC. TABLE CA Probe Name Ag5964 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gatgtgaaagtcaccaggaatct-3′ 23 1204 120 Probe TET-5′-ttaccatagcgtgtccaatgcctgag-3′-TAMRA 26 1236 121 Reverse 5′-gatattgtcaccgaacaatgtagttt-3′ 26 1264 122

[0584] TABLE CB CNS neurodegeneration v1.0 Rel. Exp. (%) Rel. Exp. (%) Ag5964, Run Ag5964, Run Tissue Name 248162714 268784143 AD 1 Hippo 8.6 11.5 AD 2 Hippo 33.7 35.8 AD 3 Hippo 3.5 7.7 AD 4 Hippo 15.0 12.6 AD 5 hippo 100.0 100.0 AD 6 Hippo 49.7 36.6 Control 2 Hippo 30.6 24.0 Control 4 Hippo 19.9 17.8 Control (Path) 3 Hippo 11.0 6.6 AD 1 Temporal Ctx 11.4 9.5 AD 2 Temporal Ctx 40.6 29.3 AD 3 Temporal Ctx 4.6 2.9 AD 4 Temporal Ctx 37.9 27.9 AD 5 Inf Temporal Ctx 97.3 59.9 AD 5 Sup Temporal Ctx 45.1 29.3 AD 6 Inf Temporal Ctx 49.3 55.9 AD 6 Sup Temporal Ctx 57.4 75.3 Control 1 Temporal Ctx 28.7 18.2 Control 2 Temporal Ctx 47.0 21.5 Control 3 Temporal Ctx 32.3 24.1 Control 4 Temporal Ctx 14.8 17.2 Control (Path) 1 Temporal Ctx 80.7 97.9 Control (Path) 2 Temporal Ctx 57.8 49.3 Control (Path) 3 Temporal Ctx 17.6 16.6 Control (Path) 4 Temporal Ctx 62.4 47.3 AD 1 Occipital Ctx 11.0 13.1 AD 2 Occipital Ctx (Missing) 0.0 0.0 AD 3 Occipital Ctx 3.9 1.1 AD 4 Occipital Ctx 34.6 18.8 AD 5 Occipital Ctx 41.5 29.3 AD 6 Occipital Ctx 41.5 41.8 Control 1 Occipital Ctx 8.5 2.2 Control 2 Occipital Ctx 66.0 48.6 Control 3 Occipital Ctx 28.5 15.4 Control 4 Occipital Ctx 7.7 13.4 Control (Path) 1 Occipital Ctx 92.0 86.5 Control (Path) 2 Occipital Ctx 21.6 12.9 Control (Path) 3 Occipital Ctx 5.8 4.9 Control (Path) 4 Occipital Ctx 19.8 10.9 Control 1 Parietal Ctx 22.5 12.9 Control 2 Parietal Ctx 40.9 24.1 Control 3 Parietal Ctx 20.4 19.1 Control (Path) 1 Parietal Ctx 95.9 72.2 Control (Path) 2 Parietal Ctx 32.3 31.4 Control (Path) 3 Parietal Ctx 4.9 12.2 Control (Path) 4 Parietal Ctx 66.4 33.0

[0585] TABLE CC General screening panel v1.5 Rel. Exp. (%) Ag5964, Run Tissue Name 248163367 Adipose 3.6 Melanoma* Hs688(A).T 0.0 Melanoma* Hs688(B).T 0.0 Melanoma* M14 0.0 Melanoma* LOXIMVI 0.0 Melanoma* SK-MEL-5 0.0 Squamous cell carcinoma SCC-4 0.0 Testis Pool 3.0 Prostate ca.* (bone met) PC-3 0.0 Prostate Pool 2.5 Placenta 0.0 Uterus Pool 5.7 Ovarian ca. OVCAR-3 0.0 Ovarian ca. SK-OV-3 0.0 Ovarian ca. OVCAR-4 0.0 Ovarian ca. OVCAR-5 0.0 Ovarian ca. IGROV-1 0.0 Ovarian ca. OVCAR-8 0.0 Ovary 0.0 Breast ca. MCF-7 0.0 Breast ca. MDA-MB-231 0.0 Breast ca. BT 549 0.0 Breast ca. T47D 0.0 Breast ca. MDA-N 0.0 Breast Pool 0.0 Trachea 5.1 Lung 0.0 Fetal Lung 7.0 Lung ca. NCI-N417 4.2 Lung ca. LX-1 0.0 Lung ca. NCI-H146 4.8 Lung ca. SHP-77 3.2 Lung ca. A549 0.0 Lung ca. NCI-H526 0.0 Lung ca. NCI-H23 0.0 Lung ca. NCI-H460 0.0 Lung ca. HOP-62 0.0 Lung ca. NCI-H522 0.0 Liver 0.0 Fetal Liver 0.7 Liver ca. HepG2 0.0 Kidney Pool 2.0 Fetal Kidney 5.6 Renal ca. 786-0 0.0 Renal ca. A498 0.0 Renal ca. ACHN 0.0 Renal ca. UO-31 0.0 Renal ca. TK-10 0.0 Bladder 8.1 Gastric ca. (liver met.) NCI-N87 0.0 Gastric ca. KATO III 0.0 Colon ca. SW-948 0.0 Colon ca. SW480 0.0 Colon ca.* (SW480 met) SW620 0.0 Colon ca. HT29 0.0 Colon ca. HCT-116 0.0 Colon ca. CaCo-2 0.0 Colon cancer tissue 0.0 Colon ca. SW1116 0.0 Colon ca. Colo-205 0.0 Colon ca. SW-48 0.0 Colon Pool 0.3 Small Intestine Pool 13.8 Stomach Pool 4.5 Bone Marrow Pool 4.3 Fetal Heart 0.5 Heart Pool 4.2 Lymph Node Pool 2.8 Fetal Skeletal Muscle 5.4 Skeletal Muscle Pool 0.7 Spleen Pool 1.0 Thymus Pool 1.3 CNS cancer (glio/astro) U87-MG 0.0 CNS cancer (glio/astro) U-118-MG 0.0 CNS cancer (neuro; met) SK-N-AS 0.4 CNS cancer (astro) SF-539 0.0 CNS cancer (astro) SNB-75 0.0 CNS cancer (glio) SNB-19 0.0 CNS cancer (glio) SF-295 0.0 Brain (Amygdala) Pool 37.4 Brain (cerebellum) 43.8 Brain (fetal) 100.0 Brain (Hippocampus) Pool 46.3 Cerebral Cortex Pool 47.6 Brain (Substantia nigra) Pool 35.4 Brain (Thalamus) Pool 61.1 Brain (whole) 46.3 Spinal Cord Pool 20.9 Adrenal Gland 2.4 Pituitary gland Pool 7.6 Salivary Gland 2.3 Thyroid (female) 0.0 Pancreatic ca. CAPAN2 0.0 Pancreas Pool 1.3

[0586] CNS_neurodegeneration_v1.0 Summary: Ag5964 Two experiments with same probe-primer sets are in good agreement. This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this receptor may be of use in reversing the dementia/memory loss associated with this disease and neuronal death.

[0587] General_screening_panel_v1.5 Summary: Ag5964 Expression of this gene is seen exclusively in all the regions of brain region, with highest expression in fetal brain (CT=30.9). Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0588] D. CG165528-02 (NOV9b): Neurexin I Beta.

[0589] Expression of gene CG165528-02 was assessed using the primer-probe set Ag7944, described in Table DA. Results of the RTQ-PCR runs are shown in Table DB. TABLE DA Probe Name Ag7944 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gcaccacatccaccatttc-3′ 119 213 123 Probe TET-5′-cagcagcaagcatcattcagtgcc-3′-TAMRA 24 237 124 Reverse 5′-gatgccggtgacctgtaga-3′ 19 269 125

[0590] TABLE DB CNS neurodegeneration v1.0 Rel. Exp. (%) Ag7944, Run Tissue Name 319510463 AD 1 Hippo 5.9 AD 2 Hippo 13.2 AD 3 Hippo 3.5 AD 4 Hippo 4.7 AD 5 Hippo 100.0 AD 6 Hippo 31.6 Control 2 Hippo 15.9 Control 4 Hippo 3.8 Control (Path) 3 Hippo 2.4 AD 1 Temporal Ctx 9.2 AD 2 Temporal Ctx 31.4 AD 3 Temporal Ctx 6.4 AD 4 Temporal Ctx 23.8 AD 5 Inf Temporal Ctx 79.0 AD 5 Sup Temporal Ctx 20.0 AD 6 Inf Temporal Ctx 30.8 AD 6 Sup Temporal Ctx 40.3 Control 1 Temporal Ctx 2.7 Control 2 Temporal Ctx 33.4 Control 3 Temporal Ctx 19.8 Control 3 Temporal Ctx 7.7 Control (Path) 1 Temporal Ctx 44.8 Control (Path) 2 Temporal Ctx 47.6 Control (Path) 3 Temporal Ctx 4.7 Control (Path) 4 Temporal Ctx 48.3 AD 1 Occipital Ctx 17.4 AD 2 Occipital Ctx (Missing) 0.0 AD 3 Occipital Ctx 3.3 AD 4 Occipital Ctx 23.8 AD 5 Occipital Ctx 56.6 AD 6 Occipital Ctx 16.2 Control 1 Occipital Ctx 1.7 Control 2 Occipital Ctx 64.6 Control 3 Occipital Ctx 22.7 Control 4 Occipital Ctx 2.4 Control (Path) 1 Occipital Ctx 72.2 Control (Path) 2 Occipital Ctx 12.9 Control (Path) 3 Occipital Ctx 0.9 Control (Path) 4 Occipital Ctx 23.3 Control 1 Parietal Ctx 5.8 Control 2 Parietal Ctx 37.4 Control 3 Parietal Ctx 16.6 Control (Path) 1 Parietal Ctx 81.8 Control (Path) 2 Parietal Ctx 28.1 Control (Path) 3 Parietal Ctx 1.8 Control (Path) 4 Parietal Ctx 62.4

[0591] CNS_neurodegeneration_v1.0 Summary: Ag7944 No differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, this panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0592] Panel 4.1D Summary: Ag7944 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0593] E. CG165666-01 (NOV10a): CG1-87 Protein.

[0594] Expression of gene CG165666-01 was assessed using the primer-probe set Ag5963, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB, EC and ED. TABLE EA Probe Name Ag5963 Start SEQ ID Primers Seqences Length Position No Forward 5′-gagacaagtcctaaatgccgac-3′ 22 159 126 Probe TET-5′-aacaatcttttgttggattgaaacagctaatcct-3′-TAMRA 34 188 127 Reverse 5′-ctagtagtgccagcctgacaaa-3′ 22 226 128

[0595] TABLE EB CNS neurodegeneration v1.0 Rel. Exp. (%) Ag5963, Run Tissue Name 248162713 AD 1 Hippo 10.7 AD 2 Hippo 28.7 AD 3 Hippo 7.5 AD 4 Hippo 7.4 AD 5 Hippo 100.0 AD 6 Hippo 50.0 Control 2 Hippo 29.7 Control 4 Hippo 13.6 Control (Path) 3 Hippo 4.8 AD 1 Temporal Ctx 27.4 AD 2 Temporal Ctx 39.0 AD 3 Temporal Ctx 4.2 AD 4 Temporal Ctx 23.2 AD 5 Inf Temporal Ctx 72.7 AD 5 Sup Temporal Ctx 40.6 AD 6 Inf Temporal Ctx 46.3 AD 6 Sup Temporal Ctx 42.6 Control 1 Temporal Ctx 5.4 Control 2 Temporal Ctx 29.9 Control 3 Temporal Ctx 9.3 Control 3 Temporal Ctx 8.7 Control (Path) 1 Temporal Ctx 51.4 Control (Path) 2 Temporal Ctx 36.6 Control (Path) 3 Temporal Ctx 3.8 Control (Path) 4 Temporal Ctx 27.5 AD 1 Occipital Ctx 12.6 AD 2 Occipital Ctx (Missing) 0.0 AD 3 Occipital Ctx 6.4 AD 4 Occipital Ctx 16.8 AD 5 Occipital Ctx 54.3 AD 6 Occipital Ctx 16.4 Control 1 Occipital Ctx 3.3 Control 2 Occipital Ctx 57.4 Control 3 Occipital Ctx 13.7 Control 4 Occipital Ctx 6.3 Control (Path) 1 Occipital Ctx 84.1 Control (Path) 2 Occipital Ctx 11.0 Control (Path) 3 Occipital Ctx 3.0 Control (Path) 4 Occipital Ctx 21.8 Control 1 Parietal Ctx 8.0 Control 2 Parietal Ctx 25.3 Control 3 Parietal Ctx 14.5 Control (Path) 1 Parietal Ctx 63.3 Control (Path) 2 Parietal Ctx 24.8 Control (Path) 3 Parietal Ctx 1.9 Control (Path) 4 Parietal Ctx 34.9

[0596] TABLE EC General screening panel v1.5 Rel. Exp. (%) Ag5963, Run Tissue Name 247945158 Adipose 9.9 Melanoma* Hs688(A).T 56.6 Melanoma* Hs688(B).T 30.4 Melanoma* M14 15.7 Melanoma* LOXIMVI 60.7 Melanoma* SK-MEL-5 20.9 Squamous cell carcinoma SCC-4 12.6 Testis Pool 15.3 Prostate ca.* (bone met) PC-3 42.9 Prostate Pool 24.5 Placenta 5.3 Uterus Pool 14.2 Ovarian ca. OVCAR-3 49.3 Ovarian ca. SK-OV-3 7.8 Ovarian ca. OVCAR-4 6.9 Ovarian ca. OVCAR-5 26.1 Ovarian ca. IGROV-1 28.9 Ovarian ca. OVCAR-8 10.1 Ovary 5.2 Breast ca. MCF-7 26.6 Breast ca. MDA-MB-231 31.9 Breast ca. BT 549 16.8 Breast ca. T47D 4.3 Breast ca. MDA-N 13.5 Breast Pool 26.4 Trachea 16.2 Lung 0.0 Fetal Lung 47.0 Lung ca. NCI-N417 2.9 Lung ca. LX-1 35.6 Lung ca. NCI-H146 8.8 Lung ca. SHP-77 61.1 Lung ca. A549 95.3 Lung ca. NCI-H526 3.0 Lung ca. NCI-H23 34.9 Lung ca. NCI-H460 21.0 Lung ca. HOP-62 9.0 Lung ca. NCI-H522 15.1 Liver 2.2 Fetal Liver 10.2 Liver ca. HepG2 15.6 Kidney Pool 14.1 Fetal Kidney 23.0 Renal ca. 786-0 12.1 Renal ca. A498 6.6 Renal ca. ACHN 42.3 Renal ca. UO-31 3.8 Renal ca. TK-10 21.2 Bladder 8.8 Gastric ca. (liver met.) NCI-N87 100.0 Gastric ca. KATO III 84.1 Colon ca. SW-948 9.1 Colon ca. SW480 24.8 Colon ca.* (SW480 met) SW620 19.5 Colon ca. HT29 13.6 Colon ca. HCT-116 65.5 Colon ca. CaCo-2 23.0 Colon cancer tissue 23.0 Colon ca. SW1116 5.2 Colon ca. Colo-205 16.7 Colon ca. SW-48 6.1 Colon Pool 8.5 Small Intestine Pool 9.9 Stomach Pool 8.0 Bone Marrow Pool 7.8 Fetal Heart 13.9 Heart Pool 17.7 Lymph Node Pool 0.0 Fetal Skeletal Muscle 5.0 Skeletal Muscle Pool 50.0 Spleen Pool 17.1 Thymus Pool 13.0 CNS cancer (glio/astro) U87-MG 27.9 CNS cancer (glio/astro) U-118-MG 88.9 CNS cancer (neuro; met) SK-N-AS 72.7 CNS cancer (astro) SF-539 38.7 CNS cancer (astro) SNB-75 77.4 CNS cancer (glio) SNB-19 9.7 CNS cancer (glio) SF-295 70.2 Brain (Amygdala) Pool 29.5 Brain (cerebellum) 47.3 Brain (fetal) 41.8 Brain (Hippocampus) Pool 6.2 Cerebral Cortex Pool 33.2 Brain (Substantia nigra) Pool 10.2 Brain (Thalamus) Pool 13.3 Brain (whole) 12.1 Spinal Cord Pool 6.4 Adrenal Gland 6.2 Pituitary gland Pool 2.1 Salivary Gland 25.3 Thyroid (female) 5.7 Pancreatic ca. CAPAN2 14.3 Pancreas Pool 30.6

[0597] Table ED. Panel 4.1D TABLE ED Panel 4.1D Rel. Exp. (%) Ag5963, Run Tissue Name 247851482 Secondary Th1 act 47.0 Secondary Th2 act 55.5 Secondary Tr1 act 15.3 Secondary Th1 rest 0.0 Secondary Th2 rest 0.0 Secondary Tr1 rest 0.0 Primary Th1 act 4.8 Primary Th2 act 34.6 Primary Tr1 act 29.5 Primary Th1 rest 0.0 Primary Th2 rest 11.4 Primary Tr1 rest 0.0 CD45RA CD4 lymphocyte act 45.1 CD45RO CD4 lymphocyte act 55.5 CD8 lymphocyte act 2.8 Secondary CD8 lymphocyte rest 27.2 Secondary CD8 lymphocyte act 0.0 CD4 lymphocyte none 2.7 2ry Th1/Th2/Tr1_anti-CD95 0.0 CH11 LAK cells rest 13.5 LAK cells IL-2 9.0 LAK cells IL-2 + IL-12 0.0 LAK cells IL-2 + IFN gamma 12.6 LAK cells IL-2 + IL-18 12.3 LAK cells PMA/ionomycin 13.6 NK Cells IL-2 rest 48.3 Two Way MLR 3 day 10.9 Two Way MLR 5 day 0.0 Two Way MLR 7 day 0.0 PBMC rest 0.0 PBMC PWM 5.5 PBMC PHA-L 5.8 Ramos (B cell) none 3.9 Ramos (B cell) ionomycin 21.6 B lymphocytes PWM 40.3 B lymphocytes CD40L and IL-4 57.0 EOL-1 dbcAMP 43.2 EOL-1 dbcAMP PMA/ionomycin 6.5 Dendritic cells none 11.8 Dendritic cells LPS 0.0 Dendritic cells anti-CD40 8.7 Monocytes rest 6.4 Monocytes LPS 21.3 Macrophages rest 12.5 Macrophages LPS 0.0 HUVEC none 21.3 HUVEC starved 41.2 HUVEC IL-1beta 27.9 HUVEC IFN gamma 31.0 HUVEC TNF alpha + IFN gamma 0.0 HUVEC TNF alpha + IL4 0.0 HUVEC IL-11 9.5 Lung Microvascular EC none 84.7 Lung Microvascular EC TNFalpha + 17.4 IL-1beta Microvascular Dermal EC none 0.0 Microsvasular Dermal EC TNFalpha + 5.5 IL-1beta Bronchial epithelium TNFalpha + 22.1 IL1beta Small airway epithelium none 53.2 Small airway epithelium TNFalpha + 54.0 IL-1beta Coronery artery SMC rest 30.1 Coronery artery SMC TNFalpha + 36.1 IL-1beta Astrocytes rest 0.0 Astrocytes TNFalpha + IL-1beta 0.0 KU-812 (Basophil) rest 24.1 KU-812 (Basophil) PMA/ionomycin 47.3 CCD1106 (Keratinocytes) none 32.5 CCD1106 (Keratinocytes) TNFalpha + 35.6 IL-1beta Liver cirrhosis 10.0 NCI-H292 none 20.9 NCI-H292 IL-4 39.0 NCI-H292 IL-9 47.0 NCI-H292 IL-13 69.3 NCI-H292 IFN gamma 17.4 HPAEC none 3.8 HPAEC TNF alpha + IL-1 beta 34.4 Lung fibroblast none 31.0 Lung fibroblast TNF alpha + IL-1 beta 33.0 Lung fibroblast IL-4 12.4 Lung fibroblast IL-9 21.6 Lung fibroblast IL-13 0.0 Lung fibroblast IFN gamma 42.9 Dermal fibroblast CCD1070 rest 69.7 Dermal fibroblast CCD1070 TNF 100.0 alpha Dermal fibroblast CCD1070 IL-1 beta 37.1 Dermal fibroblast IFN gamma 6.7 Dermal fibroblast IL-4 32.8 Dermal Fibroblasts rest 39.0 Neutrophils TNFa + LPS 0.0 Neutrophils rest 24.8 Colon 0.0 Lung 0.0 Thymus 5.1 Kidney 23.3

[0598] CNS_neurodegeneration_v1.0 Summary: Ag5963 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Blockade of this receptor may be of use in the treatment of this disease and decrease neuronal death.

[0599] General_screening_panel_v1.5 Summary: Ag5963 Higest expression of this gene is detected in a gastric cancer NC1—N87 cell line (CT=31). Moderate to low levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0600] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0601] In addition, this gene is expressed at moderate to low levels in all regions of the central nervous system examined, including amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0602] Panel 4.1D Summary: Ag5963 Low expression of this gene is detected in TNF alpha activated dermal fibroblast (CT=34.6). Therefore, theratpeutic modulation of this gene may be useful in the treatment of skin disorders, including psoriasis.

[0603] F. CG165676-01(NOV11a): Integrin Alpha-2 Precursor.

[0604] Expression of gene CG165676-01 was assessed using the primer-probe set Ag4510, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB, FC and FD. TABLE FA Probe Name Ag4510 Start SEQ ID Primers Sequnces Length Position No Forward 5′-aaaatttcaggcacaccaaag-3′ 21 3018 129 Probe TET-5′-aattgaactgcagaactgcttcctgt-3′-TAMRA 26 3039 130 Reverse 5′-tctcctttcatgtgaacgtctt-3′ 22 3087 131

[0605] TABLE FB AI comprehensive panel v1.0 Rel. Exp. (%) Ag4510, Run Tissue Name 46953623 110967 COPD-F 5.8 110980 COPD-F 8.8 110968 COPD-M 3.8 110977 COPD-M 29.7 110989 Emphysema-F 37.9 110992 Emphysema-F 8.4 110993 Emphysema-F 5.4 110994 Emphysema-F 2.1 110995 Emphysema-F 22.4 110996 Emphysema-F 6.7 110997 Asthma-M 8.2 111001 Asthma-F 16.6 111002 Asthma-F 26.6 111003 Atopic Asthma-F 32.8 111004 Atopic Asthma-F 32.5 111005 Atopic Asthma-F 24.0 111006 Atopic Asthma-F 5.1 111417 Allergy-M 14.8 112347 Allergy-M 0.0 112349 Normal Lung-F 0.0 112357 Normal Lung-F 16.3 112354 Normal Lung-M 5.7 112374 Crohns-F 5.3 112389 Match Control Crohns-F 31.6 112375 Crohns-F 5.4 112732 Match Control Crohns-F 22.7 112725 Crohns-M 3.3 112387 Match Control Crohns-M 5.4 112378 Crohns-M 0.0 112390 Match Control Crohns-M 60.3 112726 Crohns-M 27.9 112731 Match Control Crohns-M 12.0 112380 Ulcer Col-F 23.3 112734 Match Control Ulcer Col-F 65.5 112384 Ulcer Col-F 63.3 112737 Match Control Ulcer Col-F 13.2 112386 Ulcer Col-F 2.0 112738 Match Control Ulcer Col-F 25.3 112381 Ulcer Col-M 0.4 112735 Match Control Ulcer Col-M 2.1 112382 Ulcer Col-M 35.6 112394 Match Control Ulcer Col-M 1.2 112383 Ulcer Col-M 39.0 112736 Match Control Ulcer Col-M 16.3 112423 Psoriasis-F 12.3 112427 Match Control Psoriasis-F 38.2 112418 Psoriasis-M 6.4 112723 Match Control Psoriasis-M 5.3 112419 Psoriasis-M 6.4 112424 Match Control Psoriasis-M 7.3 112420 Psoriasis-M 25.9 112425 Match Control Psoriasis-M 35.6 104689 (MF) OA Bone-Backus 82.4 104690 (MF) Adj “Normal” 16.6 Bone-Backus 104691 (MF) OA Synovium-Backus 19.5 104692 (BA) OA Cartilage-Backus 1.7 104694 (BA) OA Bone-Backus 100.0 104695 (BA) Adj “Normal” 28.9 Bone-Backus 104696 (BA) OA Synovium-Backus 12.8 104700 (SS) OA Bone-Backus 15.4 104701 (SS) Adj “Normal” 19.6 Bone-Backus 104702 (SS) OA Synovium-Backus 32.8 117093 OA Cartilage Rep7 17.2 112672 OA Bone5 16.8 112673 OA Synovium5 11.8 112674 OA Synovial Fluid cells5 8.0 117100 OA Cartilage Rep14 0.8 112756 OA Bone9 30.8 112757 OA Synovium9 3.2 112758 OA Synovial Fluid Cells9 8.1 117125 RA Cartilage Rep2 9.9 113492 Bone2 RA 50.0 113493 Synovium2 RA 16.6 113494 Syn Fluid Cells RA 25.5 113499 Cartilage4 RA 28.5 113500 Bone4 RA 42.6 113501 Synovium4 RA 30.1 113502 Syn Fluid Cells4 RA 15.9 113495 Cartilage3 RA 25.2 113496 Bone3 RA 34.4 113497 Synovium3 RA 17.4 113498 Syn Fluid Cells3 RA 45.1 117106 Normal Cartilage Rep20 1.5 113663 Bone3 Normal 0.1 113664 Synovium3 Normal 0.0 113665 Syn Fluid Cells3 Normal 0.0 117107 Normal Cartilage Rep22 5.6 113667 Bone4 Normal 7.5 113668 Synovium4 Normal 6.0 113669 Syn Fluid Cells4 Normal 9.1

[0606] TABLE FC General screening panel v1.4 Rel. Exp. (%) Ag4510, Run Tissue Name 222695870 Adipose 1.7 Melanoma* Hs688(A).T 0.9 Melanoma* Hs688(B).T 4.3 Melanoma* M14 5.6 Melanoma* LOXIMVI 40.3 Melanoma* SK-MEL-5 4.3 Squamous cell carcinoma SCC-4 22.1 Testis Pool 0.9 Prostate ca.* (bone met) PC-3 36.3 Prostate Pool 2.3 Placenta 0.2 Uterus Pool 0.4 Ovarian ca. OVCAR-3 1.4 Ovarian ca. SK-OV-3 2.2 Ovarian ca. OVCAR-4 0.7 Ovarian ca. OVCAR-5 10.4 Ovarian ca. IGROV-1 7.4 Ovarian ca. OVCAR-8 1.2 Ovary 0.8 Breast ca. MCF-7 19.3 Breast ca. MDA-MB-231 64.6 Breast ca. BT 549 0.0 Breast ca. T47D 17.0 Breast ca. MDA-N 3.2 Breast Pool 1.8 Trachea 6.6 Lung 0.2 Fetal Lung 7.2 Lung ca. NCI-N417 0.0 Lung ca. LX-1 6.0 Lung ca. NCI-H146 0.8 Lung ca. SHP-77 0.0 Lung ca. A549 10.8 Lung ca. NCI-H526 0.2 Lung ca. NCI-H23 9.9 Lung ca. NCI-H460 1.0 Lung ca. HOP-62 17.9 Lung ca. NCI-H522 0.1 Liver 0.0 Fetal Liver 0.6 Liver ca. HepG2 16.7 Kidney Pool 1.7 Fetal Kidney 7.1 Renal ca. 786-0 1.1 Renal ca. A498 2.0 Renal ca. ACHN 1.0 Renal ca. UO-31 8.5 Renal ca. TK-10 9.2 Bladder 8.0 Gastric ca. (liver met.) NCI-N87 35.1 Gastric ca. KATO III 21.0 Colon ca. SW-948 3.5 Colon ca. SW480 12.8 Colon ca.* (SW480 met) SW620 5.6 Colon ca. HT29 2.9 Colon ca. HCT-116 10.4 Colon ca. CaCo-2 5.7 Colon cancer tissue 17.0 Colon ca. SW1116 1.5 Colon ca. Colo-205 2.7 Colon ca. SW-48 3.5 Colon Pool 1.6 Small Intestine Pool 1.9 Stomach Pool 2.3 Bone Marrow Pool 0.9 Fetal Heart 1.1 Heart Pool 0.4 Lymph Node Pool 1.5 Fetal Skeletal Muscle 1.4 Skeletal Muscle Pool 0.1 Spleen Pool 4.2 Thymus Pool 2.0 CNS cancer (glio/astro) U87-MG 23.3 CNS cancer (glio/astro) U-118-MG 18.7 CNS cancer (neuro; met) SK-N-AS 24.0 CNS cancer (astro) SF-539 0.2 CNS cancer (astro) SNB-75 1.9 CNS cancer (glio) SNB-19 6.9 CNS cancer (glio) SF-295 100.0 Brain (Amygdala) Pool 1.9 Brain (cerebellum) 0.1 Brain (fetal) 0.8 Brain (Hippocampus) Pool 1.4 Cerebral Cortex Pool 1.6 Brain (Substantia nigra) Pool 2.0 Brain (Thalamus) Pool 2.3 Brain (whole) 0.4 Spinal Cord Pool 2.4 Adrenal Gland 3.7 Pituitary gland Pool 0.2 Salivary Gland 0.7 Thyroid (female) 1.0 Pancreatic ca. CAPAN2 34.2 Pancreas Pool 1.9

[0607] TABLE FD Panel 4.1D Rel. Exp. (%) Ag4510, Run Tissue Name 246789401 Secondary Th1 act 9.8 Secondary Th2 act 10.7 Secondary Tr1 act 2.4 Secondary Th1 rest 0.1 Secondary Th2 rest 0.2 Secondary Tr1 rest 0.0 Primary Th1 act 0.0 Primary Th2 act 0.9 Primary Tr1 act 1.4 Primary Th1 rest 0.0 Primary Th2 rest 0.3 Primary Tr1 rest 0.1 CD45RA CD4 lymphocyte act 16.8 CD45RO CD4 lymphocyte act 0.8 CD8 lymphocyte act 0.0 Secondary CD8 lymphocyte rest 0.8 Secondary CD8 lymphocyte act 0.4 CD4 lymphocyte none 0.0 2ry Th1/Th2/Tr1_anti-CD95 CH11 0.1 LAK cells rest 0.0 LAK cells IL-2 0.4 LAK cells IL-2 + IL-12 0.0 LAK cells IL-2 + IFN gamma 0.6 LAK cells IL-2 + IL-18 0.2 LAK cells PMA/ionomycin 3.7 NK Cells IL-2 rest 1.9 Two Way MLR 3 day 0.1 Two Way MLR 5 day 0.1 Two Way MLR 7 day 0.7 PBMC rest 0.0 PBMC PWM 0.2 PBMC PHA-L 0.1 Ramos (B cell) none 0.0 Ramos (B cell) ionomycin 0.0 B lymphocytes PWM 0.8 B lymphocytes CD40L and IL-4 0.2 EOL-1 dbcAMP 0.0 EOL-1 dbcAMP PMA/ionomycin 2.8 Dendritic cells none 0.0 Dendritic cells LPS 0.0 Dendritic cells anti-CD40 0.0 Monocytes rest 0.0 Monocytes LPS 0.8 Macrophages rest 0.0 Macrophages LPS 0.1 HUVEC none 18.0 HUVEC starved 14.2 HUVEC IL-1beta 36.1 HUVEC IFN gamma 22.8 HUVEC TNF alpha + IFN gamma 3.1 HUVEC TNF alpha + IL4 2.5 HUVEC IL-11 17.2 Lung Microvascular EC none 79.0 Lung Microvascular EC TNFalpha + IL-1beta 11.2 Microvascular Dermal EC none 1.9 Microsvasular Dermal EC TNFalpha + IL-1beta 3.6 Bronchial epithelium TNFalpha + IL1beta 26.4 Small airway epithelium none 15.7 Small airway epithelium TNFalpha + IL-1beta 42.3 Coronery artery SMC rest 27.0 Coronery artery SMC TNFalpha + IL-1beta 45.4 Astrocytes rest 0.3 Astrocytes TNFalpha + IL-1beta 2.0 KU-812 (Basophil) rest 0.0 KU-812 (Basophil) PMA/ionomycin 1.5 CCD1106 (Keratinocytes) none 48.0 CCD1106 (Keratinocytes) TNFalpha + IL-1beta 35.1 Liver cirrhosis 2.4 NCI-H292 none 22.2 NCI-H292 IL-4 16.0 NCI-H292 IL-9 30.8 NCI-H292 IL-13 20.4 NCI-H292 IFN gamma 13.5 HPAEC none 12.0 HPAEC TNF alpha + IL-1 beta 64.2 Lung fibroblast none 27.2 Lung fibroblast TNF alpha + IL-1 beta 55.5 Lung fibroblast IL-4 35.8 Lung fibroblast IL-9 42.6 Lung fibroblast IL-13 2.6 Lung fibroblast IFN gamma 100.0 Dermal fibroblast CCD1070 rest 31.2 Dermal fibroblast CCD1070 TNF alpha 40.3 Dermal fibroblast CCD1070 IL-1 beta 26.1 Dermal fibroblast IFN gamma 3.8 Dermal fibroblast IL-4 1.8 Dermal Fibroblasts rest 2.8 Neutrophils TNFa + LPS 0.0 Neutrophils rest 0.0 Colon 0.5 Lung 2.2 Thymus 0.6 Kidney 7.1

[0608] AI_comprehensive panel_v1.0 Summary: Ag4510 Highest expression of this gene is detected in orthoarthritis bone (CT=29.5). This gene shows a widespread expression in this panel. Moderate to low levels of expression of this gene are detected in samples derived from normal and orthoarthitis/rheumatoid arthritis bone, cartilage, synovium and synovial fluid samples, from normal lung, COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn's disease (normal matched control and diseased), ulcerative colitis (normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis

[0609] General_screening_panel_v1.4 Summary: Ag4510 Highest expression of this gene is detected in a CNS cancer SF-295 cell line (CT=25.6). Moderate to high levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Expression of this gene is higher in cancer cell lines compared to the normal tissues. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0610] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, fetal skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0611] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0612] Interestingly, this gene is expressed at much higher levels in fetal (CT=31-33) when compared to adult liver and skeletal muscle (CTs=35-38). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver and skeletal muscle. In addition, the relative overexpression of this gene in fetal tissues suggest that the protein product may enhance liver and muscle growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver and muscle related diseases.

[0613] Panel 4.1D Summary: Ag4510 Highest expression of this gene is detected in a IFN gamma stimulated lung fibroblasts (CT=28.4). Moderate to low levels of expression of this gene is detected in endothelial cells, keratinocytes, dermal fibroblasts and lung related samples including resting and activated-NCI-H292 mucoepidermoid cells, resting and activated lung fibroblasts, human pulmonary aortic endothelial cells (treated and untreated), small airway epithelium (treated and untreated), treated bronchial epithelium and lung microvascular endothelial cells (treated and untreated). Low expression of this gene is also detected in activated secondary Th1, Th2 and Tr1 cells, activated eosinophils and activated CD45RA CD4 lymphocyte (CT=30.9), which represent activated naive T cells. In activated memory T cells (CD45RO CD4 lymphocyte) or CD4 Th1 or Th2 cells, resting CD4 cells (CTs>35), the expression of this gene is strongly down regulated suggesting a role for this putative protein in differentiation or activation of naive T cells. Therefore, therapeutic modulation of this gene may be useful in the treatement of autoimune and inflammatory disorders that include arthritis, psoriasis, Crohns disease, ulcerative colitis, asthma, chronic obstructive pulmonary disease, allergy and emphysema.

[0614] G. CG165719-01 (NOV12d), CG165719-02 (NOV12b) and CG165719-03 (NOV12c): Neuronal Membrane Glycoprotein M6-B.

[0615] Expression of gene CG165719-01, CG165719-02 and CG165719-03 was assessed using the primer-probe sets Ag5977, Ag5978, Ag7810 and Ag7794, described in Tables GA, GB, GC and GD. Results of the RTQ-PCR runs are shown in Tables GE, GF and GG. Please note that primer-probe set Ag5977 is specific for CG165719-03 and Ag5978 is specific for CG165719-01 and CG165719-02. TABLE GA Probe Name Ag5977 Start SEQ ID Primers Sequeces Length Position No Forward 5′-caagagagaaaaggctgctttg-3′ 22 109 132 Probe TET-5′-ggaggagtcccctacgcctccct-3′-TAMRA 23 151 133 Reverse 5′-cacagccgcagaataaggc-3′ 19 205 134

[0616] TABLE GB Probe Name Ag5978 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gtgaacagcagagctgaaatg-3′ 21 121 135 Probe TET-5′-cccgtgccaaccctgggggacag-3′-TAMRA 23 196 136 Reverse 5′-ggggactcctcccagac-3′ 17 266 137

[0617] TABLE GC Probe Name Ag7810 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gcatcagtggaatgttcgttt-3′ 21 572 138 Probe TET-5′-cagccaggccactccaagcacat-3′-TAMRA 23 602 139 Reverse 5′-caccgctgagaaaccaaac-3′ 19 630 140

[0618] TABLE GD Probe Name Ag7794 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gcgattcttgagcaacactt-3′ 20 370 141 Probe TET-5′-cacctcgctcagcaaggcatggt-3′-TAMRA 33 407 142 Reverse 5′-ccatagatgacatactgcatcagtt-3′ 25 434 143

[0619] TABLE GE CNS neurodegeneration v1.0 Rel. Exp. (%) Rel. Exp. (%) Rel. Exp. (%) Ag5977, Run Ag5978, Run Ag7794, Run Tissue Name 248589057 248589058 312372407 AD 1 Hippo 16.3 8.5 15.0 AD 2 Hippo 40.9 28.7 23.3 AD 3 Hippo 5.5 4.7 5.0 AD 4 Hippo 10.3 8.4 10.0 AD 5 hippo 28.3 65.1 10.8 AD 6 Hippo 100.0 26.6 74.7 Control 2 Hippo 42.0 38.2 22.2 Control 4 Hippo 15.4 17.2 13.4 Control (Path) 6.2 4.0 4.8 3 Hippo AD 1 Temporal Ctx 11.8 5.4 15.3 AD 2 Temporal Ctx 44.8 34.2 23.0 AD 3 Temporal Ctx 3.6 3.8 0.0 AD 4 Temporal Ctx 26.2 22.1 15.5 AD 5 Inf Temporal 39.0 82.9 100.0 Ctx AD 5 Sup Temporal 24.8 45.7 56.3 Ctx AD 6 Inf Temporal 74.7 47.6 45.1 Ctx AD 6 Sup Temporal 69.3 36.6 38.7 Ctx Control 1 Temporal 9.3 8.7 6.0 Ctx Control 2 Temporal 58.2 52.9 23.8 Ctx Control 3 Temporal 20.7 14.8 9.0 Ctx Control 4 Temporal 17.8 14.8 9.1 Ctx Control (Path) 1 0.2 75.3 24.0 Temporal Ctx Control (Path) 2 30.6 29.9 17.2 Temporal Ctx Control (Path) 3 4.5 2.6 4.5 Temporal Ctx Control (Path) 4 26.2 24.5 12.6 Temporal Ctx AD 1 Occipital Ctx 9.6 3.0 10.7 AD 2 Occipital Ctx 0.0 0.0 0.0 (Missing) AD 3 Occipital Ctx 4.2 1.5 5.0 AD 4 Occipital Ctx 19.2 21.6 12.6 AD 5 Occipital Ctx 42.0 13.2 12.1 AD 6 Occipital Ctx 31.4 46.7 19.1 Control 1 2.2 1.7 2.1 Occipital Ctx Control 2 56.3 84.1 32.8 Occipital Ctx Control 3 15.0 11.0 9.4 Occipital Ctx Control 4 9.9 9.3 6.2 Occipital Ctx Control (Path) 1 0.1 100.0 42.6 Occipital Ctx Control (Path) 2 7.4 6.4 5.5 Occipital Ctx Control (Path) 3 2.4 1.2 2.7 Occipital Ctx Control (Path) 4 5.6 4.9 4.7 Occipital Ctx Control 1 5.5 5.6 7.1 Parietal Ctx Control 2 18.3 26.8 31.0 Parietal Ctx Control 3 18.2 17.1 10.2 Parietal Ctx Control (Path) 1 0.1 92.7 36.9 Parietal Ctx Control (Path) 2 17.7 18.4 11.4 Parietal Ctx Control (Path) 3 2.7 1.2 3.2 Parietal Ctx Control (Path) 4 24.1 22.1 12.4 Parietal Ctx

[0620] TABLE GF General screening panel v1.5 Rel. Exp. (%) Rel. Exp. (%) Ag5977, Run Ag5978, Run Tissue Name 248220118 248445832 Adipose 0.3 0.1 Melanoma* Hs688(A).T 0.0 0.0 Melanoma* Hs688(B).T 0.0 0.0 Melanoma* M14 0.7 3.4 Melanoma* LOXIMVI 0.0 0.0 Melanoma* SK-MEL-5 2.1 11.7 Squamous cell 0.0 0.0 carcinoma SCC-4 Testis Pool 0.5 0.8 Prostate ca.* 0.0 0.0 (bone met) PC-3 Prostate Pool 2.8 2.0 Placenta 0.0 0.0 Uterus Pool 2.3 1.0 Ovarian ca. OVCAR-3 0.1 0.2 Ovarian ca. SK-OV-3 0.0 0.1 Ovarian ca. OVCAR-4 0.0 0.0 Ovarian ca. OVCAR-5 0.1 0.0 Ovarian ca. IGROV-1 54.0 24.7 Ovarian ca. OVCAR-8 3.9 5.9 Ovary 0.0 0.0 Breast ca. MCF-7 0.0 0.0 Breast ca. MDA-MB-231 0.0 0.0 Breast ca. BT 549 0.0 0.0 Breast ca. T47D 0.0 0.0 Breast ca. MDA-N 0.2 1.8 Breast Pool 0.1 0.1 Trachea 2.2 0.6 Lung 0.3 0.3 Fetal Lung 0.8 1.2 Lung ca. NCI-N417 0.0 0.3 Lung ca. LX-1 0.0 0.0 Lung ca. NCI-H146 0.2 1.7 Lung ca. SHP-77 0.0 0.0 Lung ca. A549 0.0 0.0 Lung ca. NCI-H526 0.1 0.0 Lung ca. NCI-H23 0.0 0.1 Lung ca. NCI-H460 0.0 0.0 Lung ca. HOP-62 0.0 0.0 Lung ca. NCI-H522 0.0 0.0 Liver 0.0 0.0 Fetal Liver 0.0 0.0 Liver ca. HepG2 0.0 0.0 Kidney Pool 0.4 1.1 Fetal Kidney 0.1 0.1 Renal ca. 786-0 0.0 0.0 Renal ca. A498 0.0 0.0 Renal ca. ACHN 0.0 0.0 Renal ca. UO-31 0.0 0.0 Renal ca. TK-10 0.0 0.0 Bladder 0.6 0.7 Gastric ca. (liver 0.1 0.0 met.) NCI-N87 Gastric ca. KATO III 0.0 0.0 Colon ca. SW-948 0.0 0.0 Colon ca. SW480 0.0 0.0 Colon ca.* (SW480 0.0 0.0 met) SW620 Colon ca. HT29 0.0 0.0 Colon ca. HCT-116 0.0 0.0 Colon ca. CaCo-2 0.0 0.0 Colon cancer tissue 0.0 0.0 Colon ca. SW1116 0.0 0.0 Colon ca. Colo-205 0.0 0.0 Colon ca. SW-48 0.0 0.0 Colon Pool 0.3 0.1 Small Intestine Pool 1.9 2.6 Stomach Pool 1.3 1.1 Bone Marrow Pool 0.8 1.2 Fetal Heart 0.7 0.5 Heart Pool 0.7 1.1 Lymph Node Pool 0.4 0.9 Fetal Skeletal Muscle 0.3 0.5 Skeletal Muscle Pool 1.1 1.0 Spleen Pool 0.1 0.7 Thymus Pool 0.1 0.5 CNS cancer (glio/astro) 0.0 0.0 U87-MG CNS cancer (glio/astro) 0.0 0.0 U-118-MG CNS cancer (neuro; met) 0.0 0.3 SK-N-AS CNS cancer (astro) 0.0 0.0 SF-539 CNS cancer (astro) 62.9 46.3 SNB-75 CNS cancer (glio) 73.2 27.9 SNB-19 CNS cancer (glio) 0.0 0.0 SF-295 Brain (Amygdala) Pool 84.1 43.2 Brain (cerebellum) 98.6 100.0 Brain (fetal) 53.6 24.8 Brain (Hippocampus) Pool 100.0 45.4 Cerebral Cortex Pool 89.5 54.0 Brain (Substantia nigra) 94.6 41.5 Pool Brain (Thalamus) Pool 87.1 70.2 Brain (whole) 57.4 48.6 Spinal Cord Pool 57.4 27.0 Adrenal Gland 0.4 0.4 Pituitary gland Pool 1.3 1.2 Salivary Gland 0.4 0.8 Thyroid (female) 0.3 0.1 Pancreatic ca. CAPAN2 0.0 0.0 Pancreas Pool 0.4 0.6

[0621] TABLE GG Panel 4.1D Rel. Exp. (%) Rel. Exp. (%) Rel. Exp. (%) Ag578, Run Ag7794, Run Ag7810, Run Tissue Name 248122633 312355978 312363384 Secondary Th1 act 0.0 0.0 0.0 Secondary Th2 act 0.0 0.0 0.0 Secondary Tr1 act 0.0 0.0 0.0 Secondary Th1 rest 0.0 0.0 0.0 Secondary Th2 rest 0.0 0.0 0.0 Secondary Tr1 rest 0.0 0.0 0.0 Primary Th1 act 0.0 0.0 0.0 Primary Th2 act 0.0 0.0 0.0 Primary Tr1 act 0.0 0.0 0.0 Primary Th1 rest 0.0 0.0 0.0 Primary Th2 rest 0.0 0.0 0.0 Primary Tr1 rest 0.0 0.0 0.0 CD45RA CD4 0.0 0.0 0.0 lymphocyte act CD45RO CD4 0.0 0.0 0.0 lymphocyte act CD8 lymphocyte act 0.0 0.0 0.0 Secondary CD8 0.0 0.0 0.0 lymphocyte rest Secondary CD8 0.0 0.0 0.0 lymphocyte act CD4 lymphocyte none 0.0 0.8 0.0 2ry Th1/Th2/Tr1_(—) 0.0 0.0 0.0 anti-CD95 CH11 LAK cells rest 0.0 0.0 0.0 LAK cells IL-2 0.0 0.0 0.0 LAK cells IL-2 + 0.0 0.0 0.0 IL-12 LAK cells IL-2 + 0.0 0.0 0.0 IFN gamma LAK cells IL-2 + 0.0 0.0 0.0 IL-18 LAK cells 0.0 0.0 0.0 PMA/ionomycin NK Cells IL-2 0.0 0.0 2.3 rest Two Way MLR 3 0.0 0.0 0.0 day Two Way MLR 5 0.0 0.0 0.0 day Two Way MLR 7 0.0 0.8 0.0 day PBMC rest 0.0 0.0 0.0 PBMC PWM 0.0 0.0 0.0 PBMC PHA-L 0.0 0.0 0.0 Ramos (B cell) 0.0 0.0 0.0 none Ramos (B cell) 0.0 0.0 0.0 ionomycin B lymphocytes 0.0 0.0 0.0 PWM B lymphocytes 0.0 0.0 0.0 CD40L and IL-4 EOL-1 dbcAMP 0.0 0.0 0.0 EOL-1 dbcAMP 0.0 0.0 0.0 PMA/ionomycin Dendritic cells 0.0 0.0 0.0 none Dendritic cells 0.0 0.0 0.0 LPS Dendritic cells 0.0 0.0 0.0 anti-CD40 Monocytes rest 0.0 0.0 0.0 Monocytes LPS 0.0 0.0 0.0 Macrophages rest 0.0 0.0 0.0 Macrophages LPS 0.0 0.0 0.0 HUVEC none 0.0 0.0 0.0 HUVEC starved 0.0 0.0 0.0 HUVEC IL-1beta 0.0 0.0 0.0 HUVEC IFN gamma 0.0 0.0 0.0 HUVEC TNF 0.0 0.0 0.0 alpha + IFN gamma HUVEC TNF 0.0 0.0 0.0 alpha + IL4 HUVEC IL-11 0.0 1.4 0.0 Lung Microvascular 0.0 0.0 0.0 EC none Lung Microvascular 0.0 0.0 0.0 EC TNFalpha + IL-1beta Microvascular 0.0 0.0 0.0 Dermal EC none Microsvasular 0.0 0.4 0.0 Dermal EC TNFalpha + IL-1beta Bronchial 0.0 0.0 0.0 epithelium TNFalpha + IL1beta Small airway 0.0 1.7 4.9 epithelium none Small airway 0.0 0.0 0.0 epithelium TNFalpha + IL-1beta Coronery artery 0.0 3.0 0.0 SMC rest Coronery artery 0.0 0.0 2.3 SMC TNFalpha + IL-1beta Astrocytes rest 100.0 100.0 100.0 Astrocytes 15.3 14.7 34.2 TNFalpha + IL-1beta KU-812 (Basophil) 0.0 0.0 0.0 rest KU-812 (Basophil) 0.0 0.0 0.0 PMA/ionomycin CCD1106 0.0 11.9 40.3 (Keratinocytes) none CCD1106 0.0 1.0 1.1 (Keratinocytes) TNFalpha + IL-1beta Liver cirrhosis 0.0 4.5 8.8 NCI-H292 none 0.0 0.0 0.0 NCI-H292 IL-4 0.0 0.0 0.0 NCI-H292 IL-9 0.0 3.0 0.0 NCI-H292 IL-13 0.0 0.0 5.5 NCI-H292 IFN 0.0 0.0 0.0 gamma HPAEC none 0.0 0.0 0.0 HPAEC TNF 0.0 2.3 7.9 alpha + IL-1 beta Lung fibroblast 0.0 11.6 35.8 none Lung fibroblast 0.0 7.1 7.8 TNF alpha + IL-1 beta Lung fibroblast 0.0 5.7 3.0 IL-4 Lung fibroblast 0.0 3.6 11.4 IL-9 Lung fibroblast 0.0 4.5 5.4 IL-13 Lung fibroblast 27.0 19.1 58.2 IFN gamma Dermal fibroblast 0.0 8.1 1.6 CCD1070 rest Dermal fibroblast 29.1 4.0 1.5 CCD1070 TNF alpha Dermal fibroblast 0.0 2.9 0.0 CCD1070 IL-1 beta Dermal fibroblast 0.0 5.2 19.9 IFN gamma Dermal fibroblast 0.0 8.5 32.3 IL-4 Dermal Fibroblasts 0.0 0.9 2.6 rest Neutrophils TNFa 0.0 0.0 0.0 + LPS Neutrophils rest 0.0 0.0 0.0 Colon 16.0 10.1 1.1 Lung 0.0 6.0 8.0 Thymus 0.0 0.0 0.0 Kidney 0.0 10.3 64.6

[0622] CNS_neurodegeneration_v1.0 Summary: Ag5977/Ag5978/Ag7794 Three experiments with different probe pimer sets are in good agreement. This panel confirms the expression of this gene at significant levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0623] General_screening_panel_v1.5 Summary: Ag5977/Ag5978 Two experminents with different probe primer sets are in good agreement with highest expression of this gene seen in cerebellum and hippocampus (CTs=27-28.9). This gene shows preferential expression in all the regions of brain including including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0624] Moderate expression of this gene is also seen in two of the brain cancer, two ovarian cancer and melanoma cell lines. Therefore, therapeutic modulation of this gene may be useful in the treatment of melanoma, brain, and ovarian cancers.

[0625] Low levels of expression of this gene is also seen in pancreas, pituitary gland, skeletal muscle and gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0626] Panel 4.1D Summary: Ag5978/Ag7794/Ag7810 Multiple experiments with different probe-primer sets are in good agreement. Highest expression of this gene is detected in resting astrocytes (CTs=31-34.7). Low expression of this gene is also seen in activated astrocytes and lung fibroblasts. Therefore, therapeutic regulation of this gene or the encoded protein could be important in the treatment of multiple sclerosis or other inflammatory diseases of the CNS and and inflammatory lung disorders including chronic obstructive pulmonary disease, asthma, allergy and emphysema.

[0627] Ag5977 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0628] H. CG167488-01 (NOV13b): Hypothetical Transmembrane Protein.

[0629] Expression of gene CG167488-01 was assessed using the primer-probe set Ag5997, described in Table HA. Results of the RTQ-PCR runs are shown in Tables HB, HC and HD. TABLE HA Probe Name Ag5997 Start SEQ ID Primers Sequnces Length Position No Forward 5′-gagctaccttataaagaccatctgtacat-3′ 29 3 144 Probe TET-5′-ccactgtgaaatggagtttcaaaatcaca-3′-TAMRA 29 32 145 Reverse 5′-atatgtgctcctagtcttatgttcatgt-3′ 28 73 146

[0630] TABLE HB CNS_neurodegeneration_v1.0 Rel. Exp. (%) Ag5997 Run Tissue Name 248589037 AD 1 Hippo 0.0 AD 2 Hippo 28.9 AD 3 Hippo 1.6 AD 4 Hippo 16.4 AD 5 hippo 92.7 AD 6 Hippo 31.4 Control 2 Hippo 35.4 Control 4 Hippo 16.8 Control (Path) 3 Hippo 28.9 AD 1 Temporal Ctx 4.6 AD 2 Temporal Ctx 35.4 AD 3 Temporal Ctx 9.1 AD 4 Temporal Ctx 30.1 AD 5 Inf Temporal Ctx 83.5 AD 5 Sup Temporal Ctx 68.8 AD 6 Inf Temporal Ctx 88.3 AD 6 Sup Temporal Ctx 59.5 Control 1 Temporal Ctx 1.2 Control 2 Temporal Ctx 34.2 Control 3 Temporal Ctx 36.3 Control 4 Temporal Ctx 13.8 Control (Path) 1 Temporal Ctx 90.8 Control (Path) 2 Temporal Ctx 52.9 Control (Path) 3 Temporal Ctx 2.6 Control (Path) 4 Temporal Ctx 54.3 AD 1 Occipital Ctx 4.6 AD 2 Occipital Ctx (Missing) 0.0 AD 3 Occipital Ctx 0.0 AD 4 Occipital Ctx 36.1 AD 5 Occipital Ctx 48.0 AD 6 Occipital Ctx 41.5 Control 1 Occipital Ctx 0.0 Control 2 Occipital Ctx 45.4 Control 3 Occipital Ctx 20.0 Control 4 Occipital Ctx 3.3 Control (Path) 1 Occipital Ctx 99.3 Control (Path) 2 Occipital Ctx 12.9 Control (Path) 3 Occipital Ctx 0.0 Control (Path) 4 Occipital Ctx 31.2 Control 1 Parietal Ctx 1.5 Control 2 Parietal Ctx 47.6 Control 3 Parietal Ctx 20.6 Control (Path) 1 Parietal Ctx 100.0 Control (Path) 2 Parietal Ctx 29.9 Control (Path) 3 Parietal Ctx 0.0 Control (Path) 4 Parietal Ctx 75.3

[0631] TABLE HC General_screening_panel_v1.5 Rel. Exp. (%) Ag5997, Run Tissue Name 248592793 Adipose 36.3 Melanoma* Hs688(A).T 2.9 Melanoma* Hs688(B).T 7.2 Melanoma* M14 0.0 Melanoma* LOXIMVI 3.4 Melanoma* SK-MEL-5 3.5 Squamous cell carcinoma SCC-4 5.4 Testis Pool 8.2 Prostate ca.* (bone met) PC-3 5.0 Prostate Pool 13.2 Placenta 8.8 Uterus Pool 5.9 Ovarian ca. OVCAR-3 12.6 Ovarian ca. SK-OV-3 22.1 Ovarian ca. OVCAR-4 3.1 Ovarian ca. OVCAR-5 25.9 Ovarian ca. IGROV-1 6.0 Ovarian ca. OVCAR-8 7.2 Ovary 1.6 Breast ca. MCF-7 0.6 Breast ca. MDA-MB-231 30.6 Breast ca. BT 549 7.9 Breast ca. T47D 0.0 Breast ca. MDA-N 0.1 Breast Pool 13.8 Trachea 12.1 Lung 0.5 Fetal Lung 100.0 Lung ca. NCI-N417 0.0 Lung ca. LX-1 3.4 Lung ca. NCI-H146 4.1 Lung ca. SHP-77 12.4 Lung ca. A549 10.3 Lung ca. NCI-H526 0.0 Lung ca. NCI-H23 6.0 Lung ca. NCI-H460 7.6 Lung ca. HOP-62 3.9 Lung ca. NCI-H522 11.5 Liver 0.0 Fetal Liver 1.8 Liver ca. HepG2 1.3 Kidney Pool 10.8 Fetal Kidney 5.6 Renal ca. 786-0 10.9 Renal ca. A498 3.8 Renal ca. ACHN 4.3 Renal ca. UO-31 7.9 Renal ca. TK-10 9.2 Bladder 14.2 Gastric ca. (liver met.) NCI-N87 22.4 Gastric ca. KATO III 12.5 Colon ca. SW-948 6.2 Colon ca. SW480 10.7 Colon ca.* (SW480 met) SW620 1.5 Colon ca. HT29 7.3 Colon ca. HCT-116 12.3 Colon ca. CaCo-2 4.2 Colon cancer tissue 11.8 Colon ca. SW1116 3.0 Colon ca. Colo-205 0.0 Colon ca. SW-48 0.4 Colon Pool 12.2 Small Intestine Pool 5.2 Stomach Pool 13.4 Bone Marrow Pool 3.7 Fetal Heart 0.8 Heart Pool 7.0 Lymph Node Pool 9.7 Fetal Skeletal Muscle 3.2 Skeletal Muscle Pool 18.0 Spleen Pool 1.3 Thymus Pool 6.7 CNS cancer (glio/astro) U87-MG 12.8 CNS cancer (glio/astro) U-118-MG 14.8 CNS cancer (neuro; met) SK-N-AS 0.0 CNS cancer (astro) SF-539 6.8 CNS cancer (astro) SNB-75 7.7 CNS cancer (glio) SNB-19 5.1 CNS cancer (glio) SF-295 14.9 Brain (Amygdala) Pool 5.4 Brain (cerebellum) 3.5 Brain (fetal) 0.1 Brain (Hippocampus) Pool 6.8 Cerebral Cortex Pool 7.7 Brain (Substantia nigra) Pool 4.0 Brain (Thalamus) Pool 10.7 Brain (whole) 6.3 Spinal Cord Pool 5.9 Adrenal Gland 0.1 Pituitary gland Pool 5.8 Salivary Gland 2.3 Thyroid (female) 6.6 Pancreatic ca. CAPAN2 21.8 Pancreas Pool 17.2

[0632] TABLE HD Panel 5D Rel. Exp. (%) Ag5997, Run 263248222 97457_Patient-02go_adipose 13.4 97476_Patient-07sk_skeletal muscle 0.0 97477_Patient-07ut_uterus 0.0 97478_Patient-07pl_placenta 22.8 97481_Patient-08sk_skeletal muscle 1.6 97482_Patient-08ut_uterus 0.0 97483_Patient-08pl_placenta 11.2 97486_Patient-09sk_skeletal muscle 0.0 97487_Patient-09ut_uterus 13.8 97488_Patient-09pl_placenta 0.0 97492_Patient-10ut_uterus 29.5 97493_Patient-10pl_placenta 0.0 97495_Patient-11go_adipose 17.7 97496_Patient-11sk_skeletal muscle 0.0 97497_Patient-11ut_uterus 58.6 97498_Patient-11pl_placenta 100.0 97500_Patient-12go_adipose 0.0 97501_Patient-12sk_skeletal muscle 0.0 97502_Patient-12ut_uterus 5.9 97503_Patient-12pl_placenta 6.2 94721_Donor 2 U - A_Mesenchymal Stem Cells 0.0 94722_Donor 2 U - B_Mesenchymal Stem Cells 0.0 94723_Donor 2 U - C_Mesenchymal Stem Cells 0.0 94709_Donor 2 AM - A_adipose 0.0 94710_Donor 2 AM - B_adipose 9.5 94711_Donor 2 AM - C_adipose 0.0 94712_Donor 2 AD - A_adipose 0.0 94713_Donor 2 AD - B_adipose 7.2 94714_Donor 2 AD - C_adipose 0.0 94742_Donor 3 U - A_Mesenchymal Stem Cells 0.0 94743_Donor 3 U - B_Mesenchymal Stem Cells 5.6 94730_Donor 3 AM - A_adipose 4.5 94731_Donor 3 AM - B_adipose 0.0 94732_Donor 3 AM - C_adipose 3.2 94733_Donor 3 AD - A_adipose 0.0 94734_Donor 3 AD - B_adipose 0.0 94735_Donor 3 AD - C_adipose 9.2 77138_Liver_HepG2untreated 8.2 73556_Heart_Cardiac stromal cells (primary) 0.0 81735_Small Intestine 5.4 72409_Kidney_Proximal Convoluted Tubule 2.5 82685_Small intestine_Duodenum 0.0 90650_Adrenal_Adrenocortical adenoma 0.0 72410_Kidney_HRCE 21.2 72411_Kidney_HRE 5.8 73139_Uterus_Uterine smooth muscle cells 0.0

[0633] CNS_neurodegeneration_v1.0 Summary: Ag5997 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0634] General_screeningpanel_v1.5 Summary: Ag5997 Highest expression of this gene is detected in fetal lung (CT=29.4). Interestingly, this gene is expressed at much higher levels in fetal compared to adult lung (CT=37). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung related diseases.

[0635] Moderate to low levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0636] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, thyroid, pituitary gland, skeletal muscle, heart, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0637] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0638] Panel 5D Summary: Ag5997 Low expression of this gene is exclusively seen in placenta of non-diabetic but obese patient (CT=33.9). Therefore, expression of this gene may be used to distinguish placenta from other samples used in this panel.

[0639] I. CG50970-01 (NOV15b) and CG50970-02 (NOV15i): Glypican-2 precursor.

[0640] Expression of gene CG50970-01 and CG50970-03 was assessed using the primer-probe sets Ag1309 and Ag2251, described in Tables IA and IB. Results of the RTQ-PCR runs are shown in Tables IC, ID, IE, IF, IG, IH, II, IJ and IK. Please note that CG50970-03 represents a full-length physical clone. TABLE IA Probe Name Ag1309 Start SEQ ID Primers Sequnces Length Position No Forward 5′-actctctgacccagctcttctc-3′ 22 359 147 Probe TET-5′-ccactcctacggccgcctgtatg-3′-TAMRA 23 381 148 Reverse 5′-gagaacaggccattgaatatga-3′ 22 416 149

[0641] TABLE IB Probe Name Ag2251 Start SEQ ID Primers Sequnces Length Position No Forward 5′-actctctgacccagctcttctc-3′ 22 359 150 Probe TET-5′-ccactcctacggccgcctgtatg-3′-TAMRA 23 381 151 Reverse 5′-gagaacaggccattgaatatga-3′ 22 416 152

[0642] TABLE IC AI_comprehensive panel_v1.0 Rel. Exp. (%) Ag2251, Run Tissue Name 44570248 110967 COPD-F 20.7 110980 COPD-F 6.0 110968 COPD-M 4.4 110977 COPD-M 8.8 110989 Emphysema-F 12.6 110992 Emphysema-F 2.9 110993 Emphysema-F 16.4 110994 Emphysema-F 3.8 110995 Emphysema-F 19.3 110996 Emphysema-F 2.4 110997 Asthma-M 5.6 111001 Asthma-F 14.8 111002 Asthma-F 16.4 111003 Atopic Asthma-F 16.2 111004 Atopic Asthma-F 28.3 111005 Atopic Asthma-F 7.2 111006 Atopic Asthma-F 4.4 111417 Allergy-M 11.0 112347 Allergy-M 7.5 112349 Normal Lung-F 9.4 112357 Normal Lung-F 34.2 112354 Normal Lung-M 9.2 112374 Crohns-F 10.3 112389 Match Control Crohns-F 6.0 112375 Crohns-F 22.2 112732 Match Control Crohns-F 7.5 112725 Crohns-M 0.0 112387 Match Control Crohns-M 3.0 112378 Crohns-M 10.4 112390 Match Control Crohns-M 40.6 112726 Crohns-M 6.7 112731 Match Control Crohns-M 9.0 112380 Ulcer Col-F 25.5 112734 Match Control Ulcer Col-F 9.5 112384 Ulcer Col-F 22.2 112737 Match Control Ulcer Col-F 5.3 112386 Ulcer Col-F 0.0 112738 Match Control Ulcer Col-F 0.0 112381 Ulcer Col-M 2.0 112735 Match Control Ulcer Col-M 6.9 112382 Ulcer Col-M 15.8 112394 Match Control Ulcer Col-M 5.6 112383 Ulcer Col-M 13.3 112736 Match Control Ulcer Col-M 2.3 112423 Psoriasis-F 4.1 112427 Match Control Psoriasis-F 29.3 112418 Psoriasis-M 4.7 112723 Match Control Psoriasis-M 27.9 112419 Psoriasis-M 2.1 112424 Match Control Psoriasis-M 2.9 112420 Psoriasis-M 20.4 112425 Match Control Psoriasis-M 23.8 104689 (MF) OA Bone-Backus 8.7 104690 (MF) Adj “Normal” Bone-Backus 8.4 104691 (MF) OA Synovium-Backus 4.3 104692 (BA) OA Cartilage-Backus 2.4 104694 (BA) OA Bone-Backus 4.6 104695 (BA) Adj “Normal” Bone-Backus 7.7 104696 (BA) OA Synovium-Backus 2.7 104700 (SS) OA Bone-Backus 9.0 104701 (SS) Adj “Normal” Bone-Backus 3.8 104702 (SS) OA Synovium-Backus 7.5 117093 OA Cartilage Rep7 14.7 112672 OA Bone5 57.0 112673 OA Synovium5 27.9 112674 OA Synovial Fluid cells5 24.8 117100 OA Cartilage Rep14 4.0 112756 OA Bone9 100.0 112757 OA Synovium9 17.9 112758 OA Synovial Fluid Cells9 9.2 117125 RA Cartilage Rep2 6.9 113492 Bone2 RA 3.7 113493 Synovium2 RA 0.6 113494 Syn Fluid Cells RA 3.0 113499 Cartilage4 RA 1.3 113500 Bone4 RA 2.2 113501 Synovium4 RA 2.8 113502 Syn Fluid Cells4 RA 5.3 113495 Cartilage3 RA 0.0 113496 Bone3 RA 2.9 113497 Synovium3 RA 0.0 113498 Syn Fluid Cells3 RA 0.0 117106 Normal Cartilage Rep20 0.0 113663 Bone3 Normal 10.3 113664 Synovium3 Normal 6.5 113665 Syn Fluid Cells3 Normal 3.6 117107 Normal Cartilage Rep22 10.5 113667 Bone4 Normal 9.3 113668 Synovium4 Normal 22.7 113669 Syn Fluid Cells4 Normal 12.2

[0643] TABLE ID CNS_neurodegeneration_v1.0 Rel. Exp. (%) Ag225, Run Tissue Name 206265375 AD 1 Hippo 19.8 AD 2 Hippo 35.8 AD 3 Hippo 7.2 AD 4 Hippo 9.7 AD 5 hippo 59.0 AD 6 Hippo 97.9 Control 2 Hippo 37.1 Control 4 Hippo 34.9 Control (Path) 3 Hippo 17.2 AD 1 Temporal Ctx 20.6 AD 2 Temporal Ctx 33.7 AD 3 Temporal Ctx 9.9 AD 4 Temporal Ctx 36.1 AD 5 Inf Temporal Ctx 76.8 AD 5 Sup Temporal Ctx 97.9 AD 6 Inf Temporal Ctx 59.9 AD 6 Sup Temporal Ctx 100.0 Control 1 Temporal Ctx 9.9 Control 2 Temporal Ctx 29.9 Control 3 Temporal Ctx 10.5 Control 4 Temporal Ctx 34.2 Control (Path) 1 Temporal Ctx 63.7 Control (Path) 2 Temporal Ctx 13.8 Control (Path) 3 Temporal Ctx 3.5 Control (Path) 4 Temporal Ctx 34.2 AD 1 Occipital Ctx 19.5 AD 2 Occipital Ctx (Missing) 0.0 AD 3 Occipital Ctx 17.3 AD 4 Occipital Ctx 19.2 AD 5 Occipital Ctx 52.9 AD 6 Occipital Ctx 42.0 Control 1 Occipital Ctx 6.3 Control 2 Occipital Ctx 51.8 Control 3 Occipital Ctx 23.0 Control 4 Occipital Ctx 6.6 Control (Path) 1 Occipital Ctx 73.7 Control (Path) 2 Occipital Ctx 16.8 Control (Path) 3 Occipital Ctx 11.8 Control (Path) 4 Occipital Ctx 28.1 Control 1 Parietal Ctx 12.1 Control 2 Parietal Ctx 62.4 Control 3 Parietal Ctx 20.4 Control (Path) 1 Parietal Ctx 43.8 Control (Path) 2 Parietal Ctx 14.9 Control (Path) 3 Parietal Ctx 7.8 Control (Path) 4 Parietal Ctx 29.9

[0644] TABLE IE General_screening_panel_v1.5 Rel. Exp. (%) Ag2251, Run Tissue Name 246733742 Adipose 0.2 Melanoma* Hs688(A).T 0.8 Melanoma* Hs688(B).T 0.9 Melanoma* M14 4.5 Melanoma* LOXIMVI 0.6 Melanoma* SK-MEL-5 4.3 Squamous cell carcinoma SCC-4 0.4 Testis Pool 8.1 Prostate ca.* (bone met) PC-3 3.6 Prostate Pool 0.0 Placenta 0.7 Uterus Pool 0.1 Ovarian ca. OVCAR-3 2.9 Ovarian ca. SK-OV-3 0.5 Ovarian ca. OVCAR-4 0.6 Ovarian ca. OVCAR-5 1.2 Ovarian ca. IGROV-1 5.5 Ovarian ca. OVCAR-8 1.6 Ovary 0.8 Breast ca. MCF-7 1.6 Breast ca. MDA-MB-231 0.2 Breast ca. BT 549 22.5 Breast ca. T47D 0.2 Breast ca. MDA-N 2.6 Breast Pool 1.3 Trachea 0.3 Lung 0.4 Fetal Lung 2.9 Lung ca. NCI-N417 5.0 Lung ca. LX-1 5.3 Lung ca. NCI-H146 62.9 Lung ca. SHP-77 12.4 Lung ca. A549 1.5 Lung ca. NCI-H526 25.9 Lung ca. NCI-H23 7.0 Lung ca. NCI-H460 6.7 Lung ca. HOP-62 1.3 Lung ca. NCI-H522 36.3 Liver 0.0 Fetal Liver 0.4 Liver ca. HepG2 0.2 Kidney Pool 0.9 Fetal Kidney 9.3 Renal ca. 786-0 0.8 Renal ca. A498 0.7 Renal ca. ACHN 1.0 Renal ca. UO-31 5.7 Renal ca. TK-10 9.2 Bladder 0.6 Gastric ca. (liver met.) NCI-N87 0.3 Gastric ca. KATO III 1.4 Colon ca. SW-948 0.1 Colon ca. SW480 3.8 Colon ca.* (SW480 met) SW620 1.6 Colon ca. HT29 0.9 Colon ca. HCT-116 2.5 Colon ca. CaCo-2 4.3 Colon cancer tissue 0.7 Colon ca. SW1116 0.7 Colon ca. Colo-205 0.2 Colon ca. SW-48 0.8 Colon Pool 0.8 Small Intestine Pool 0.9 Stomach Pool 0.4 Bone Marrow Pool 0.3 Fetal Heart 2.0 Heart Pool 0.3 Lymph Node Pool 0.8 Fetal Skeletal Muscle 2.8 Skeletal Muscle Pool 0.3 Spleen Pool 0.3 Thymus Pool 9.9 CNS cancer (glio/astro) U87-MG 3.0 CNS cancer (glio/astro) U-118-MG 0.8 CNS cancer (neuro; met) SK-N-AS 22.4 CNS cancer (astro) SF-539 0.3 CNS cancer (astro) SNB-75 17.2 CNS cancer (glio) SNB-19 7.3 CNS cancer (glio) SF-295 7.6 Brain (Amygdala) Pool 1.5 Brain (cerebellum) 3.1 Brain (fetal) 100.0 Brain (Hippocampus) Pool 1.0 Cerebral Cortex Pool 1.3 Brain (Substantia nigra) Pool 0.8 Brain (Thalamus) Pool 2.1 Brain (whole) 2.2 Spinal Cord Pool 1.7 Adrenal Gland 0.3 Pituitary gland Pool 0.1 Salivary Gland 0.2 Thyroid (female) 0.0 Pancreatic ca. CAPAN2 0.8 Pancreas Pool 0.9

[0645] TABLE IF Oncology_cell_line_screening_panel_v3.2 Rel. Exp. (%) g2251, Run Tissue Name 248202132 94905_Daoy_Medulloblastoma/Cerebellum_sscDNA 1.2 94906_TE671_Medulloblastom/Cerebellum_sscDNA 14.8 94907_D283 Med_Medulloblastoma/Cerebellum_(—) 16.6 sscDNA 94908_PFSK-1_Primitive Neuroectodermal/ 1.7 Cerebellum_sscDNA 94909_XF-498_CNS_sscDNA 1.2 94910_SNB-78_CNS/glioma_sscDNA 1.0 94911_SF-268_CNS/glioblastoma_sscDNA 1.8 94912_T98G_Glioblastoma_sscDNA 1.3 96776_SK-N-SH_Neuroblastoma (metastasis)_(—) 11.7 sscDNA 94913_SF-295_CNS/glioblastoma_sscDNA 1.4 132565_NT2 pool_sscDNA 16.6 94914_Cerebellum_sscDNA 1.3 96777_Cerebellum_sscDNA 1.7 94916_NCI-H292_Mucoepidermoid lung carcinoma_(—) 0.3 sscDNA 94917_DMS-114_Small cell lung cancer_sscDNA 24.7 94918_DMS-79_Small cell lung cancer/ 100.0 neuroendocrine_sscDNA 94919_NCI-H146_Small cell lung cancer/ 80.1 neuroendocrine_sscDNA 94920_NCI-H526_Small cell lung cancer/ 79.0 neuroendocrine_sscDNA 94921_NCI-N417_Small cell lung cancer/ 7.9 neuroendocrine_sscDNA 94923_NCI-H82_Small cell lung cancer/ 23.2 neuroendocrine_sscDNA 94924_NCI-H157_Squamous cell lung cancer 0.2 (metastasis)_sscDNA 94925_NCI-H1155_Large cell lung cancer/ 19.5 neuroendocrine_sscDNA 94926_NCI-H1299_Large cell lung cancer/ 9.3 neuroendocrine_sscDNA 94927_NCI-H727_Lung carcinoid_sscDNA 0.9 94928_NCI-UMC-11_Lung carcinoid_sscDNA 5.1 94929_LX-1_Small cell lung cancer_sscDNA 1.0 94930_Colo-205_Colon cancer_sscDNA 0.0 94931_KM12_Colon cancer_sscDNA 0.6 94932_KM20L2_Colon cancer_sscDNA 0.2 94933_NCI-H716_Colon cancer_sscDNA 5.6 94935_SW-48_Colon adenocarcinoma_sscDNA 0.2 94936_SW1116_Colon adenocarcinoma_sscDNA 0.3 94937_LS 174T_Colon adenocarcinoma_sscDNA 0.3 94938_SW-948_Colon adenocarcinoma_sscDNA 0.2 94939_SW-480_Colon adenocarcinoma_sscDNA 0.0 94940_NCI-SNU-5_Gastric carcinoma_sscDNA 0.9 112197_KATO III_Stomach_sscDNA 0.0 94943_NCI-SNU-16_Gastric carcinoma_sscDNA 0.2 94944_NCI-SNU-1_Gastric carcinoma_sscDNA 1.5 94946_RF-1_Gastric adenocarcinoma_sscDNA 0.3 94947_RF-48_Gastric adenocarcinoma_sscDNA 0.6 96778_MKN-45_Gastric carcinoma_sscDNA 0.6 94949_NCI-N87_Gastric carcinoma_sscDNA 0.6 94951_OVCAR-5_Ovarian carcinoma_sscDNA 0.0 94952_RL95-2_Uterine carcinoma_sscDNA 0.3 94953_HelaS3_Cervical adenocarcinoma_sscDNA 0.2 94954_Ca Ski_Cervical epidermoid carcinoma 10.7 (metastasis)_sscDNA 94955_ES-2_Ovarian clear cell carcinoma_(—) 2.1 sscDNA 94957_Ramos/6 h stim_Stimulated with PMA/ 4.0 ionomycin 6 h_sscDNA 94958_Ramos/14 h stim_Stimulated with PMA/ 2.9 ionomycin 14 h_sscDNA 94962_MEG-01_Chronic myelogenous leukemia 0.3 (megokaryoblast)_sscDNA 94963_Raji_Burkitt's lymphoma_sscDNA 1.2 94964_Daudi_Burkitt's lymphoma_sscDNA 2.4 94965_U266_B-cell plasmacytoma/myeloma_(—) 0.0 sscDNA 94968_CA46_Burkitt's lymphoma_sscDNA 3.7 94970_RL_non-Hodgkin's B-cell lymphoma_(—) 3.3 sscDNA 94972_JM1_pre-B-cell lymphoma/leukemia_(—) 5.5 sscDNA 94973_Jurkat_T cell leukemia_sscDNA 5.1 94974_TF-1_Erythroleukemia_sscDNA 1.5 94975_HUT 78_T-cell lymphoma_sscDNA 2.5 94977_U937_Histiocytic lymphoma_sscDNA 1.4 94980_KU-812_Myelogenous leukemia_sscDNA 0.0 94981_769-P_Clear cell renal carcinoma_(—) 0.0 sscDNA 94983_Caki-2_Clear cell renal carcinoma_(—) 0.1 sscDNA 94984_SW 839_Clear cell renal carcinoma_(—) 0.9 sscDNA 94986_G401_Wilms' tumor_sscDNA 0.9 126768_293 cells_sscDNA 1.9 94987_Hs766T_Pancreatic carcinoma (LN 0.7 metastasis)_sscDNA 94988_CAPAN-1_Pancreatic adenocarcinoma 0.1 (liver metastasis)_sscDNA 94989_SU86.86_Pancreatic carcinoma (liver 0.0 metastasis)_sscDNA 94990_BxPC-3_Pancreatic adenocarcinoma_(—) 0.0 sscDNA 94991_HPAC_Pancreatic adenocarcinoma_(—) 0.6 sscDNA 94992_MIA PaCa-2_Pancreatic carcinoma_(—) 0.0 sscDNA 94993_CFPAC-1_Pancreatic ductal 1.0 adenocarcinoma_sscDNA 94994_PANC-1_Pancreatic epithelioid ductal 0.2 carcinoma_sscDNA 94996_T24_Bladder carcinma (transitional 0.2 cell)_sscDNA 94997_5637_Bladder carcinoma_sscDNA 2.4 94998_HT-1197_Bladder carcinoma_sscDNA 0.7 94999_UM-UC-3_Bladder carcinma 0.2 (transitional cell)_sscDNA 95000_A204_Rhabdomyosarcoma_sscDNA 0.0 95001_HT-1080_Fibrosarcoma_sscDNA 0.0 95002_MG-63_Osteosarcoma (bone)_sscDNA 0.0 95003_SK-LMS-1_Leiomyosarcoma (vulva)_(—) 1.3 sscDNA 95004_SJRH30_Rhabdomyosarcoma (met to bone 9.9 marrow)_sscDNA 95005_A431_Epidermoid carcinoma_sscDNA 0.2 95007_WM266-4_Melanoma_sscDNA 0.9 112195_DU 145_Prostate_sscDNA 0.2 95012_MDA-MB-468_Breast adenocarcinoma_(—) 0.5 sscDNA 112196_SSC-4_Tongue_sscDNA 0.9 112194_SSC-9_Tongue_sscDNA 1.3 112191_SSC-15_Tongue_sscDNA 0.3 95017_CAL 27_Squamous cell carcinoma of 0.0 tongue_sscDNA

[0646] TABLE IG Panel 1.3D Rel. Exp. (%) Ag2251, Run Tissue Name 159074821 Liver adenocarcinoma 0.9 Pancreas 0.4 Pancreatic ca. CAPAN 2 0.4 Adrenal gland 0.6 Thyroid 0.4 Salivary gland 1.2 Pituitary gland 0.7 Brain (fetal) 73.7 Brain (whole) 4.6 Brain (amygdala) 6.4 Brain (cerebellum) 1.8 Brain (hippocampus) 22.2 Brain (substantia nigra) 2.1 Brain (thalamus) 4.5 Cerebral Cortex 3.5 Spinal cord 3.2 glio/astro U87-MG 4.3 glio/astro U-118-MG 2.2 astrocytoma SW1783 14.3 neuro*; met SK-N-AS 100.0 astrocytoma SF-539 0.5 astrocytoma SNB-75 13.0 glioma SNB-19 14.7 glioma U251 3.6 glioma SF-295 3.6 Heart (fetal) 3.4 Heart 0.0 Skeletal muscle (fetal) 15.2 Skeletal muscle 0.0 Bone marrow 1.8 Thymus 21.2 Spleen 0.8 Lymph node 1.1 Colorectal 0.8 Stomach 0.6 Small intestine 2.6 Colon ca. SW480 2.5 Colon ca.* SW620(SW480 met) 1.5 Colon ca. HT29 1.7 Colon ca. HCT-116 2.4 Colon ca. CaCo-2 2.5 Colon ca. tissue(ODO3866) 2.2 Colon ca. HCC-2998 2.0 Gastric ca.* (liver met) NCI-N87 0.8 Bladder 1.0 Trachea 1.8 Kidney 0.7 Kidney (fetal) 1.9 Renal ca. 786-0 1.0 Renal ca. A498 4.5 Renal ca. RXF 393 0.0 Renal ca. ACHN 0.3 Renal ca. UO-31 2.8 Renal ca. TK-10 3.8 Liver 0.0 Liver (fetal) 1.7 Liver ca. (hepatoblast) HepG2 1.8 Lung 0.0 Lung (fetal) 3.1 Lung ca. (small cell) LX-1 4.5 Lung ca. (small cell) NCI-H69 8.7 Lung ca. (s. cell var.) SHP-77 25.7 Lung ca. (large cell)NCI-H460 2.5 Lung ca. (non-sm. cell) A549 2.8 Lung ca. (non-s. cell) NCI-H23 12.4 Lung ca. (non-s. cell) HOP-62 1.7 Lung ca. (non-s. cl) NCI-H522 28.1 Lung ca. (squam.) SW 900 2.1 Lung ca. (squam.) NCI-H596 0.7 Mammary gland 1.0 Breast ca.* (pl. ef) MCF-7 4.0 Breast ca.* (pl. ef) MDA-MB-231 1.1 Breast ca.* (pl. ef) T47D 1.1 Breast ca. BT-549 16.3 Breast ca. MDA-N 6.4 Ovary 3.2 Ovarian ca. OVCAR-3 1.7 Ovarian ca. OVCAR-4 0.8 Ovarian ca. OVCAR-5 2.3 Ovarian ca. OVCAR-8 7.3 Ovarian ca. IGROV-1 2.4 Ovarian ca.* (ascites) SK-OV-3 0.6 Uterus 0.8 Placenta 0.8 Prostate 1.1 Prostate ca.* (bone met)PC-3 3.2 Testis 69.7 Melanoma Hs688(A).T 0.0 Melanoma* (met) Hs688(B).T 0.0 Melanoma UACC-62 0.4 Melanoma M14 2.6 Melanoma LOX IMVI 0.7 Melanoma* (met) SK-MEL-5 5.6 Adipose 0.0

[0647] TABLE IH Panel 2D Rel. Exp. (%) Ag2251, Run Tissue Name 159075939 Normal Colon 5.5 CC Well to Mod Diff (ODO3866) 4.5 CC Margin (ODO3866) 2.6 CC Gr.2 rectosigmoid (ODO3868) 1.2 CC Margin (ODO3868) 1.1 CC Mod Diff (ODO3920) 5.8 CC Margin (ODO3920) 2.3 CC Gr.2 ascend colon (ODO3921) 4.1 CC Margin (ODO3921) 0.0 CC from Partial Hepatectomy (ODO4309) Mets 1.3 Liver Margin (ODO4309) 0.0 Colon mets to lung (OD04451-01) 4.3 Lung Margin (OD04451-02) 0.0 Normal Prostate 6546-1 0.0 Prostate Cancer (OD04410) 3.4 Prostate Margin (OD04410) 0.0 Prostate Cancer (OD04720-01) 0.6 Prostate Margin (OD04720-02) 1.8 Normal Lung 061010 5.1 Lung Met to Muscle (ODO4286) 0.0 Muscle Margin (ODO4286) 0.6 Lung Malignant Cancer (OD03126) 3.9 Lung Margin (OD03126) 0.0 Lung Cancer (OD04404) 0.0 Lung Margin (OD04404) 0.6 Lung Cancer (OD04565) 0.6 Lung Margin (OD04565) 0.0 Lung Cancer (OD04237-01) 99.3 Lung Margin (OD04237-02) 2.4 Ocular Mel Met to Liver (ODO4310) 0.7 Liver Margin (ODO4310) 0.0 Melanoma Mets to Lung (OD04321) 18.0 Lung Margin (OD04321) 0.6 Normal Kidney 1.4 Kidney Ca, Nuclear grade 2 (OD04338) 8.0 Kidney Margin (OD04338) 0.0 Kidney Ca Nuclear grade 1/2 (OD04339) 2.4 Kidney Margin (OD04339) 0.0 Kidney Ca, Clear cell type (OD04340) 1.2 Kidney Margin (OD04340) 1.0 Kidney Ca, Nuclear grade 3 (OD04348) 0.0 Kidney Margin (OD04348) 0.8 Kidney Cancer (OD04622-01) 1.1 Kidney Margin (OD04622-03) 0.0 Kidney Cancer (OD04450-01) 4.6 Kidney Margin (OD04450-03) 0.6 Kidney Cancer 8120607 0.6 Kidney Margin 8120608 0.0 Kidney Cancer 8120613 0.0 Kidney Margin 8120614 0.6 Kidney Cancer 9010320 0.0 Kidney Margin 9010321 1.3 Normal Uterus 1.1 Uterus Cancer 064011 3.0 Normal Thyroid 0.6 Thyroid Cancer 064010 0.6 Thyroid Cancer A302152 0.4 Thyroid Margin A302153 2.3 Normal Breast 4.4 Breast Cancer (OD04566) 1.2 Breast Cancer (OD04590-01) 100.0 Breast Cancer Mets (OD04590-03) 1.5 Breast Cancer Metastasis (OD04655-05) 3.7 Breast Cancer 064006 6.8 Breast Cancer 1024 10.4 Breast Cancer 9100266 6.6 Breast Margin 9100265 3.4 Breast Cancer A209073 7.9 Breast Margin A209073 2.5 Normal Liver 0.0 Liver Cancer 064003 0.6 Liver Cancer 1025 0.0 Liver Cancer 1026 0.6 Liver Cancer 6004-T 0.0 Liver Tissue 6004-N 0.6 Liver Cancer 6005-T 1.1 Liver Tissue 6005-N 0.0 Normal Bladder 1.8 Bladder Cancer 1023 2.8 Bladder Cancer A302173 13.2 Bladder Cancer (OD04718-01) 0.0 Bladder Normal Adjacent (OD04718-03) 1.3 Normal Ovary 2.8 Ovarian Cancer 064008 4.3 Ovarian Cancer (OD04768-07) 4.0 Ovary Margin (OD04768-08) 0.0 Normal Stomach 0.8 Gastric Cancer 9060358 0.3 Stomach Margin 9060359 1.2 Gastric Cancer 9060395 0.0 Stomach Margin 9060394 1.5 Gastric Cancer 9060397 6.8 Stomach Margin 9060396 0.0 Gastric Cancer 064005 2.5

[0648] TABLE II Panel 4.1D Rel. Exp. (%) Ag2251, Run Tissue Name 244570228 Secondary Th1 act 12.4 Secondary Th2 act 16.0 Secondary Tr1 act 0.0 Secondary Th1 rest 0.0 Secondary Th2 rest 0.0 Secondary Tr1 rest 0.0 Primary Th1 act 0.0 Primary Th2 act 11.2 Primary Tr1 act 6.7 Primary Th1 rest 0.0 Primary Th2 rest 0.0 Primary Tr1 rest 0.0 CD45RA CD4 lymphocyte act 15.3 CD45RO CD4 lymphocyte act 27.7 CD8 lymphocyte act 0.0 Secondary CD8 lymphocyte rest 19.9 Secondary CD8 lymphocyte act 4.1 CD4 lymphocyte none 0.0 2ry Th1/Th2/Tr1_anti-CD95 CH11 5.2 LAK cells rest 0.0 LAK cells IL-2 0.0 LAK cells IL-2 + IL-12 0.0 LAK cells IL-2 + IFN gamma 0.0 LAK cells IL-2 + IL-18 2.7 LAK cells PMA/ionomycin 6.5 NK Cells IL-2 rest 5.6 Two Way MLR 3 day 3.5 Two Way MLR 5 day 0.0 Two Way MLR 7 day 2.5 PBMC rest 0.0 PBMC PWM 5.3 PBMC PHA-L 9.0 Ramos (B cell) none 0.0 Ramos (B cell) ionomycin 100.0 B lymphocytes PWM 7.3 B lymphocytes CD40L and IL-4 14.0 EOL-1 dbcAMP 24.8 EOL-1 dbcAMP PMA/ionomycin 0.0 Dendritic cells none 3.8 Dendritic cells LPS 0.0 Dendritic cells anti-CD40 0.0 Monocytes rest 0.0 Monocytes LPS 8.2 Macrophages rest 0.0 Macrophages LPS 0.0 HUVEC none 30.8 HUVEC starved 59.9 HUVEC IL-1beta 26.4 HUVEC IFN gamma 16.5 HUVEC TNF alpha + IFN gamma 3.3 HUVEC TNF alpha + IL4 8.9 HUVEC IL-11 39.8 Lung Microvascular EC none 22.2 Lung Microvascular EC TNFalpha + IL-1beta 2.9 Microvascular Dermal EC none 0.0 Microsvasular Dermal EC TNFalpha + IL-1beta 0.0 Bronchial epithelium TNFalpha + IL1beta 3.3 Small airway epithelium none 0.0 Small airway epithelium TNFalpha + IL-1beta 1.6 Coronery artery SMC rest 8.1 Coronery artery SMC TNFalpha + IL-1beta 15.1 Astrocytes rest 31.6 Astrocytes TNFalpha + IL-1beta 6.4 KU-812 (Basophil) rest 0.0 KU-812 (Basophil) PMA/ionomycin 2.9 CCD1106 (Keratinocytes) none 21.6 CCD1106 (Keratinocytes) TNFalpha + IL-1beta 16.3 Liver cirrhosis 0.0 NCI-H292 none 0.0 NCI-H292 IL-4 3.2 NCI-H292 IL-9 5.8 NCI-H292 IL-13 5.9 NCI-H292 IFN gamma 0.0 HPAEC none 3.3 HPAEC TNF alpha + IL-1 beta 8.2 Lung fibroblast none 21.3 Lung fibroblast TNF alpha + IL-1 beta 7.7 Lung fibroblast IL-4 10.7 Lung fibroblast IL-9 11.2 Lung fibroblast IL-13 0.0 Lung fibroblast IFN gamma 3.8 Dermal fibroblast CCD1070 rest 14.3 Dermal fibroblast CCD1070 TNF alpha 3.2 Dermal fibroblast CCD1070 IL-1 beta 3.7 Dermal fibroblast IFN gamma 3.7 Dermal fibroblast IL-4 5.9 Dermal Fibroblasts rest 3.3 Neutrophils TNFa + LPS 2.7 Neutrophils rest 6.6 Colon 0.0 Lung 0.0 Thymus 37.4 Kidney 0.0

[0649] TABLE IJ Panel 4D Rel. Exp. (%) Rel. Exp. (%) Ag1309, Run Ag2251, Run Tissue Name 138960659 159076647 Secondary Th1 act 1.5 1.6 Secondary Th2 act 1.0 1.2 Secondary Tr1 act 2.0 1.7 Secondary Th1 rest 1.7 0.5 Secondary Th2 rest 1.4 0.6 Secondary Tr1 rest 1.4 1.2 Primary Th1 act 1.7 2.7 Primary Th2 act 3.4 1.9 Primary Tr1 act 5.9 1.2 Primary Th1 rest 12.5 17.1 Primary Th2 rest 6.5 8.6 Primary Tr1 rest 3.7 2.4 CD45RA CD4 3.2 1.2 lymphocyte act CD45RO CD4 4.3 2.7 lymphocyte act CD8 lymphocyte act 1.1 1.9 Secondary CD8 1.7 0.9 lymphocyte rest Secondary CD8 1.1 1.0 lymphocyte act CD4 lymphocyte none 1.4 0.5 2ry Th1/Th2/Tr1_(—) 4.5 1.7 anti-CD95 CH11 LAK cells rest 1.2 1.6 LAK cells IL-2 3.1 1-8 LAK cells IL-2 + 1.8 0.7 IL-12 LAK cells IL-2 + 1.7 1.3 IFN gamma LAK cells IL-2 + 1.5 1.4 IL-18 LAK cells 0.8 0.0 PMA/ionomycin NK Cells IL-2 rest 0.9 1.1 Two Way MLR 3 day 1.6 2.3 Two Way MLR 5 day 1.7 0.3 Two Way MLR 7 day 0.8 0.4 PBMC rest 0.4 0.0 PBMC PWM 6.1 2.1 PBMC PHA-L 9.9 5.7 Ramos (B cell) 13.6 6.3 none Ramos (B cell) 34.9 24.3 ionomycin B lymphocytes PWM 7.4 7.3 B lymphocytes CD40L 2.7 4.4 and IL-4 EOL-1 dbcAMP 2.6 2.3 EOL-1 dbcAMP 0.3 1.3 PMA/ionomycin Dendritic cells none 0.5 0.8 Dendritic cells LPS 0.0 0.0 Dendritic cells 0.3 0.0 anti-CD40 Monocytes rest 0.3 0.0 Monocytes LPS 1.1 0.3 Macrophages rest 0.6 1.3 Macrophages LPS 0.0 0.0 HUVEC none 5.3 3.5 HUVEC starved 12.7 12.4 HUVEC IL-1beta 1.3 1.6 HUVEC IFN gamma 2.9 2.5 HUVEC TNF alpha + 1.5 0.1 IFN gamma HUVEC TNF alpha + 3.5 2.6 IL4 HUVEC IL-11 4.4 1.4 Lung Microvascular EC 1.3 2.3 none Lung Microvascular EC 2.1 1.7 TNFalpha + IL-1beta Microvascular Dermal 6.1 2.6 EC none Microsvasular Dermal 2.0 1.3 EC TNFalpha + IL-1beta Bronchial epithelium 2.9 1.6 TNFalpha + IL1beta Small airway epithelium 0.8 0.4 none Small airway epithelium 3.1 1.5 TNFalpha + IL-1beta Coronery artery SMC rest 1.3 1.1 Coronery artery SMC 1.4 2.0 TNFalpha + IL-1beta Astrocytes rest 17.8 22.5 Astrocytes TNFalpha + 6.2 4.7 IL-1beta KU-812 (Basophil) rest 0.3 0.2 KU-812 (Basophil) PMA/ionomycin 1.2 0.3 CCD1106 (Keratinocytes) none 3.9 3.9 CCD1106 (Keratinocytes) 19.5 3.1 TNFalpha + IL-1beta Liver cirrhosis 2.0 2.6 Lupus kidney 0.3 0.0 NCI-H292 none 0.7 0.4 NCI-H292 IL-4 1.7 0.4 NCI-H292 IL-9 0.0 1.6 NCI-H292 IL-13 0.6 1.6 NCI-H292 IFN gamma 0.0 0.3 HPAEC none 3.3 2.0 HPAEC TNF alpha + 1.6 0.6 IL-1 beta Lung fibroblast none 3.7 3.4 Lung fibroblast TNF alpha + 1.6 1.5 IL-1 beta Lung fibroblast IL-4 3.6 2.8 Lung fibroblast IL-9 2.6 3.2 Lung fibroblast IL-13 2.7 2.8 Lung fibroblast IFN gamma 0.5 1.9 Dermal fibroblast CCD1070 4.2 3.7 rest Dermal fibroblast CCD1070 2.4 4.2 TNF alpha Dermal fibroblast CCD1070 1.3 2.5 IL-1 beta Dermal fibroblast IFN gamma 0.7 0.2 Dermal fibroblast IL-4 0.7 0.8 IBD Colitis 2 0.2 0.0 IBD Crohn's 0.0 0.0 Colon 3.1 4.2 Lung 1.5 1.3 Thymus 1.6 0.3 Kidney 100.0 100.0

[0650] TABLE IK general_oncology_screening_panel_v_2.4 Rel. Exp. (%) Ag2251, Run Tissue Name 259733199 Colon cancer 1 5.4 Colon NAT 1 0.0 Colon cancer 2 3.1 Colon NAT 2 0.0 Colon cancer 3 8.8 Colon NAT 3 1.6 Colon malignant cancer 4 2.4 Colon NAT 4 0.0 Lung cancer 1 20.4 Lung NAT 1 0.0 Lung cancer 2 100.0 Lung NAT 2 0.6 Squamous cell carcinoma 3 3.6 Lung NAT 3 0.0 Metastatic melanoma 1 5.0 Melanoma 2 1.8 Melanoma 3 2.7 Metastatic melanoma 4 22.2 Metastatic melanoma 5 17.8 Bladder cancer 1 0.7 Bladder NAT 1 0.0 Bladder cancer 2 0.0 Bladder NAT 2 0.0 Bladder NAT 3 0.2 Bladder NAT 4 0.0 Prostate adenocarcinoma 1 4.8 Prostate adenocarcinoma 2 0.0 Prostate adenocarcinoma 3 1.1 Prostate adenocarcinoma 4 7.0 Prostate NAT 5 1.4 Prostate adenocarcinoma 6 0.5 Prostate adenocarcinoma 7 0.6 Prostate adenocarcinoma 8 0.0 Prostate adenocarcinoma 9 1.0 Prostate NAT 10 0.4 Kidney cancer 1 4.8 Kidney NAT 1 0.3 Kidney cancer 2 5.5 Kidney NAT 2 0.0 Kidney cancer 3 4.9 Kidney NAT 3 1.2 Kidney cancer 4 0.0 Kidney NAT 4 0.0

[0651] AI_comprehensive panel_v1.0 Summary: Ag2251 Highest expression of this gene is detected in orthoarthritis bone (CT=31.6). Low expression of this gene is also seen in in samples derived from normal and orthoarthitis bone, synovium samples, from normal lung, COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn's disease (normal matched control and diseased), ulcerative colitis (normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel diseases (Crohn's and ulcerative colitis), and osteoarthritis.

[0652] CNS_neurodegeneration_v1.0 Summary: Ag2251 Highest expression of this gene in this panel is detected in the cerebral cortex of an Alzheimer's patient (CT=32.7). While no association between the expression of this gene and the presence of Alzheimer's disease is detected in this panel, these results confirm the expression of this gene in areas that degenerate in Alzheimer's disease. Please see Panel 1.3D and 1.5 for a discussion of potential utility of this gene in the central nervous system.

[0653] General_screening_panel_v1.5 Summary: Ag2251 Highest expression of this gene is detected in fetal brain (CT=27.1). Low expression of this gene is also seen all the regions of adult brain including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Interestingly, expression of this gene is higher in fetal compared to the adult whole brain (32.6). This gene represents the human ortholog of cerebroglycan, a glycosylphosphatidylinositol (GPI)-anchored HSPG that is found in the developing rat brain. Heparan sulfate proteoglycans (HSPGs) are found on the surface of all adherent cells and participate in the binding of growth factors, extracellular matrix glycoproteins, cell adhesion molecules, and proteases and antiproteases. Unlike other known integral membrane HSPGs, including glypican and members of the syndecan family of transmembrane proteoglycans, cerebroglycan is apparently expressed in only one tissue in the rat: the nervous system and it is really present only during fetal development in immature neurons. Expression of this gene in human fetal and all the regions of adult brain regions suggest that this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0654] In addition, significant expression of this gene is also seen in number of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Expression of this gene is higher in cell lines derived especially from breast and lung cancers and also in fetal tissues including lung, heart, kidney and skeletal muscle (CTs=30-32.7) compared to respective adult tissues (CTs=33-35.5). Thus, this gene may play role growth or development of the cells, especially during tumorogenesis and may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the expression or function of this gene through the use of antibodies may be effective in the treatment of these cancers, especially breast and lung cancers.

[0655] Oncology_cell_line_screening_panel_v3.2 Summary: Ag2251 Highest expression of this gene is detected in small cell lung cancer DMS-79 cell line (CT=28.7). High expression of this gene is seen in number of cell lines derived from lung cancer. Moderate to low expression of this gene is also seen in number of cell lines derived from brain, colon, cervical, bladder and bone cancers, T and B cell lymphomas. Please see panel 1.5 and 1.3D for further discussion on the utility of this gene.

[0656] Panel 1.3D Summary: Ag2251 The highest level of expression of this gene is seen in a CNS cancer cell line SK-N-AS (CT=29.6). The gene is also expressed at higher levels in cell lines derived from lung, prostate, and breast cancers compared to the normal tissues and may play a role in these cancers. Thus, expression of this gene could be used as a marker or as a therapeutic for lung, prostate and breast cancer. In addition, therapeutic modulation of the activity of the product of this gene, through the use of peptides, antibodies, chimeric molecules or small molecule drugs, may be useful in the treatment of these cancers.

[0657] This gene is also expressed at higher levels in fetal liver, lung, skeletal muscle, and heart (CTs=32-35) when compared to the expression in adult tissues (CTs=40). These results suggest that expression of this gene could potentially be used to distinguish between the adult and fetal phenotypes of these tissues. Furthermore, the difference in expression in fetal and adult tissue may also indicate an involvement of the gene product in the differentiation processes leading to the formation of the adult organs. Therefore, the protein encoded by this gene could potentially play a role in the regeneration of these tissues in the adult.

[0658] This gene, a glypican homolog, is expressed at moderate to low levels across many regions of the brain. These regions include the hippocampus, amygdala, thalamus and cerebral cortex, all of which are key regions subject to Alzheimer's disease neurodegeneration. Furthermore, glypican is expressed in senile plaques and neurofibrillary tangles, also indicating a role in Alzheimer's disease. Therefore, the expression profile of this gene suggests that antibodies against the protein encoded by this gene can be used to distinguish neurodegenerative disease in the human brain. Furthermore, since glycopican are components of senile plaques which are thought to give rise to the dementia pathology of Alzheimer's disease, agents that target this gene and disrupt its role in senile plaques, (Ref. 1) may have utility in treating the cause and symptoms or Alzheimer's disease as well as other neurodegenerative diseases that involve this glypican.

REFERENCES

[0659] 1. Verbeek M M, Otte-Holler I, van den Born J, van den Heuvel L P, David G, Wesseling P, de Waal R M. (1999) Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain. Am J Pathol. 155:2115-25. PMID: 10595940

[0660] Panel 2D Summary: Ag2251 The highest expression of this gene is seen in a breast cancer sample (CT=30.3). The expression of this gene appears to show an association with samples derived from colon, lung, kidney, breast, bladder and gastric cancers when compared to the matched normal tissue. Thus, expression of this gene could be used as a marker for these cancers. In addition, therapeutic activity of the product of this gene, through the use of peptides, antibodies, chimeric molecules or small molecule drugs, may be useful in the treatment of colon, lung, kidney, breast, bladder and gastric cancers.

[0661] Panel 4.1D Summary: Ag2251 Highest expression of this gene is seen in ionomycin activated Ramos B cells (CT=31.4). Expression of this gene is low or undectable in resting Ramos B cells (CT=40). B cells represent a principle component of immunity and contribute to the immune response in a number of important functional roles, including antibody production. Production of antibodies against self-antigens is a major component in autoimmune disorders. In addition, low expression of this gene is also seen in eosinophils, HUVEC cells, activated secondary Th1 and Th2 cells, naive and memory T cells, lung and dermal fibroblast and thymus. Therefore, therapeutic modulation of this gene product may reduce or eliminate the symptoms of patients suffering from asthma, allergies, chronic obstructive pulmonary disease, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, osteoarthritis, systemic lupus erythematosus and other autoimmune disorders.

[0662] Panel 4D Summary: Ag2251/Ag1309 Two experiments using two different probe and primer sets produce results that are in very good agreement, with highest expression seen in the kidney (CTs=28-29). This high level of expression in the kidney suggests that expression of this gene can serve as a marker for kidney tissue. This gene is also expressed at low level in activated Ramos B cell line, in activated primary B cells, Th1 T cells, activated HUVEC and keratinocytes. This gene encodes for a protein that is a homolog of a glypican molecule, which belongs to the family of HSPG (heparan sulfate proteoglycans). Glypicans can regulate the activity of a wide variety of growth and survival factors. Therefore, therapeutic modulation of the expression or function of this gene or gene product, through the use of antibody drugs could potentially prevent T and B cell activation in the treatment of autoimmune mediated diseases such as insulin-dependent diabetes mellitus, rheumatoid arthritis, Crohn's disease, allergies, delayed type hypersensitivity, asthma, and psoriasis.

[0663] general oncology screening panel_V_(—)2.4 Summary: Ag2251 Highest expression of this gene is detected in lung cancer2 (CT=30.7). Moderate to low expression of this gene is also seen in lung cancer1, two metastatic melanoma and prostate cancer samples. Therefore, expression of this gene may be used as a diagnostic marker to detect the presence of these cancers and also, therapeutic modulation of this gene or its product through the use of antibodies or small molecule drug may be useful in the treatment of metastatic melanoma, lung and prostate cancers.

[0664] J. CG54443-07 (NOV16b): CG8841 Protein-like protein.

[0665] Expression of gene CG54443-07 was assessed using the primer-probe sets Ag2000 and Ag6688, described in Tables JA and JB. Results of the RTQ-PCR runs are shown in Tables JC, JD and JE. TABLE JA Probe Name Ag2000 Start SEQ ID Primers Sequnces Length Position No Forward 5′-actccaccaagaagatccagtt-3′ 22 527 153 Probe TET-5′-tctcttctggaagctctgcgacttca-3′-TAMRA 26 567 154 Reverse 5′-gcacgaagaagaggaatttctt-3′ 22 595 155

[0666] TABLE JB Probe Name Ag6688 Start SEQ ID Primers Sequeces Length Position No Forward 5′-ccaccaagacgcagc-3′ 15 185 156 Probe TET-5′-aagccaccgatgatgcctatg-3′-TAMRA 21 206 157 Reverse 5′-gagcaggtggttgtaggg-3′ 18 247 158

[0667] TABLE JC Panel 1.3D Rel. Exp. (%) Ag2000, Run Tissue Name 147805564 Liver adenocarcinoma 9.8 Pancreas 24.8 Pancreatic ca. CAPAN 2 1.3 Adrenal gland 3.3 Thyroid 11.0 Salivary gland 30.6 Pituitary gland 30.4 Brain (fetal) 13.0 Brain (whole) 39.2 Brain (amygdala) 23.7 Brain (cerebellum) 21.0 Brain (hippocampus) 46.7 Brain (substantia nigra) 10.4 Brain (thalamus) 33.2 Cerebral Cortex 100.0 Spinal cord 14.6 glio/astro U87-MG 0.1 glio/astro U-118-MG 0.3 astrocytoma SW1783 0.0 neuro*; met SK-N-AS 4.3 astrocytoma SF-539 0.0 astrocytoma SNB-75 35.6 glioma SNB-19 5.7 glioma U251 2.1 glioma SF-295 2.6 Heart (fetal) 44.4 Heart 3.6 Skeletal muscle (fetal) 69.3 Skeletal muscle 0.6 Bone marrow 1.8 Thymus 2.9 Spleen 14.8 Lymph node 8.6 Colorectal 18.9 Stomach 68.3 Small intestine 21.9 Colon ca. SW480 10.0 Colon ca.* SW620(SW480 met) 2.9 Colon ca. HT29 16.8 Colon ca. HCT-116 5.5 Colon ca. CaCo-2 11.6 Colon ca. tissue(ODO3866) 27.0 Colon ca. HCC-2998 17.2 Gastric ca.* (liver met) NCI-N87 48.6 Bladder 10.7 Trachea 36.1 Kidney 1.9 Kidney (fetal) 6.0 Renal ca. 786-0 0.0 Renal ca. A498 1.0 Renal ca. RXF 393 0.0 Renal ca. ACHN 1.5 Renal ca. UO-31 1.1 Renal ca. TK-10 2.4 Liver 0.7 Liver (fetal) 2.5 Liver ca. (hepatoblast) HepG2 8.8 Lung 12.9 Lung (fetal) 30.4 Lung ca. (small cell) LX-1 8.7 Lung ca. (small cell) NCI-H69 29.5 Lung ca. (s. cell var.) SHP-77 33.0 Lung ca. (large cell)NCI-H460 0.9 Lung ca. (non-sm. cell) A549 15.9 Lung ca. (non-s. cell) NCI-H23 2.3 Lung ca. (non-s. cell) HOP-62 3.3 Lung ca. (non-s. cl) NCI-H522 1.8 Lung ca. (squam.) SW 900 20.2 Lung ca. (squam.) NCI-H596 3.3 Mammary gland 40.1 Breast ca.* (pl. ef) MCF-7 42.0 Breast ca.* (pl. ef) MDA-MB-231 6.3 Breast ca.* (pl. ef) T47D 73.2 Breast ca. BT-549 0.0 Breast ca. MDA-N 0.2 Ovary 17.6 Ovarian ca. OVCAR-3 23.5 Ovarian ca. OVCAR-4 9.2 Ovarian ca. OVCAR-5 13.0 Ovarian ca. OVCAR-8 2.8 Ovarian ca. IGROV-1 1.9 Ovarian ca.* (ascites) SK-OV-3 2.7 Uterus 9.9 Placenta 27.2 Prostate 25.9 Prostate ca.* (bone met)PC-3 18.7 Testis 7.4 Melanoma Hs688(A).T 0.0 Melanoma* (met) Hs688(B).T 0.1 Melanoma UACC-62 0.0 Melanoma M14 0.0 Melanoma LOX IMVI 0.0 Melanoma* (met) SK-MEL-5 0.7 Adipose 4.3

[0668] TABLE JD Panel 2.2 Rel. Exp. (%) Ag2000, Run Tissue Name 174232799 Normal Colon 14.0 Colon cancer (OD06064) 21.3 Colon Margin (OD06064) 24.5 Colon cancer (OD06159) 7.0 Colon Margin (OD06159) 11.0 Colon cancer (OD06297-04) 8.7 Colon Margin (OD06297-05) 14.1 CC Gr.2 ascend colon (ODO3921) 9.4 CC Margin (ODO3921) 4.8 Colon cancer metastasis (OD06104) 3.1 Lung Margin (OD06104) 10.2 Colon mets to lung (OD04451-01) 10.8 Lung Margin (OD04451-02) 8.3 Normal Prostate 42.9 Prostate Cancer (OD04410) 17.2 Prostate Margin (OD04410) 10.4 Normal Ovary 7.6 Ovarian cancer (OD06283-03) 9.5 Ovarian Margin (OD06283-07) 4.7 Ovarian Cancer 064008 7.3 Ovarian cancer (OD06145) 0.4 Ovarian Margin (OD06145) 7.3 Ovarian cancer (OD06455-03) 18.0 Ovarian Margin (OD06455-07) 2.4 Normal Lung 18.6 Invasive poor diff. lung adeno (ODO4945-01 10.0 Lung Margin (ODO4945-03) 5.7 Lung Malignant Cancer (OD03126) 17.6 Lung Margin (OD03126) 3.9 Lung Cancer (OD05014A) 11.3 Lung Margin (OD05014B) 0.2 Lung cancer (OD06081) 4.2 Lung Margin (OD06081) 6.3 Lung Cancer (OD04237-01) 4.6 Lung Margin (OD04237-02) 9.1 Ocular Melanoma Metastasis 0.7 Ocular Melanoma Margin (Liver) 2.8 Melanoma Metastasis 0.3 Melanoma Margin (Lung) 9.2 Normal Kidney 2.5 Kidney Ca, Nuclear grade 2 (OD04338) 9.7 Kidney Margin (OD04338) 1.7 Kidney Ca Nuclear grade 1/2 (OD04339) 4.2 Kidney Margin (OD04339) 4.1 Kidney Ca, Clear cell type (OD04340) 2.7 Kidney Margin (OD04340) 6.7 Kidney Ca, Nuclear grade 3 (OD04348) 0.6 Kidney Margin (OD04348) 10.7 Kidney malignant cancer (OD06204B) 29.7 Kidney normal adjacent tissue (OD06204E) 3.8 Kidney Cancer (OD04450-01) 4.1 Kidney Margin (OD04450-03) 5.0 Kidney Cancer 8120613 1.3 Kidney Margin 8120614 7.6 Kidney Cancer 9010320 2.7 Kidney Margin 9010321 2.9 Kidney Cancer 8120607 9.0 Kidney Margin 8120608 3.0 Normal Uterus 9.0 Uterine Cancer 064011 4.9 Normal Thyroid 5.4 Thyroid Cancer 064010 2.8 Thyroid Cancer A302152 6.3 Thyroid Margin A302153 4.6 Normal Breast 19.6 Breast Cancer (OD04566) 15.8 Breast Cancer 1024 22.4 Breast Cancer (OD04590-01) 47.6 Breast Cancer Mets (OD04590-03) 41.2 Breast Cancer Metastasis (OD04655-05) 100.0 Breast Cancer 064006 11.1 Breast Cancer 9100266 49.0 Breast Margin 9100265 20.7 Breast Cancer A209073 18.6 Breast Margin A2090734 21.5 Breast cancer (OD06083) 81.2 Breast cancer node metastasis (OD06083) 66.0 Normal Liver 2.4 Liver Cancer 1026 4.4 Liver Cancer 1025 4.6 Liver Cancer 6004-T 3.8 Liver Tissue 6004-N 1.5 Liver Cancer 6005-T 12.1 Liver Tissue 6005-N 9.6 Liver Cancer 064003 1.5 Normal Bladder 19.6 Bladder Cancer 1023 6.3 Bladder Cancer A302173 8.7 Normal Stomach 62.4 Gastric Cancer 9060397 5.1 Stomach Margin 9060396 38.4 Gastric Cancer 9060395 21.5 Stomach Margin 9060394 43.5 Gastric Cancer 064005 11.4

[0669] TABLE JE Panel 4D Rel. Exp. (%) Ag2000, Run Tissue Name 165822435 Secondary Th1 act 0.2 Secondary Th2 act 0.3 Secondary Tr1 act 0.6 Secondary Th1 rest 0.1 Secondary Th2 rest 0.7 Secondary Tr1 rest 0.3 Primary Th1 act 0.1 Primary Th2 act 0.2 Primary Tr1 act 0.1 Primary Th1 rest 0.4 Primary Th2 rest 0.2 Primary Tr1 rest 0.1 CD45RA CD4 lymphocyte act 0.3 CD45RO CD4 lymphocyte act 0.7 CD8 lymphocyte act 0.8 Secondary CD8 lymphocyte rest 0.9 Secondary CD8 lymphocyte act 0.0 CD4 lymphocyte none 2.7 2ry Th1/Th2/Tr1_anti-CD95 CH11 0.0 LAK cells rest 1.4 LAK cells IL-2 2.6 LAK cells IL-2 + IL-12 1.4 LAK cells IL-2 + IFN gamma 1.2 LAK cells IL-2 + IL-18 1.6 LAK cells PMA/ionomycin 0.3 NK Cells IL-2 rest 0.4 Two Way MLR 3 day 1.2 Two Way MLR 5 day 0.4 Two Way MLR 7 day 0.0 PBMC rest 0.8 PBMC PWM 0.2 PBMC PHA-L 0.3 Ramos (B cell) none 0.5 Ramos (B cell) ionomycin 0.7 B lymphocytes PWM 0.8 B lymphocytes CD40L and IL-4 5.8 EOL-1 dbcAMP 0.0 EOL-1 dbcAMP PMA/ionomycin 0.0 Dendritic cells none 0.2 Dendritic cells LPS 0.0 Dendritic cells anti-CD40 0.0 Monocytes rest 0.0 Monocytes LPS 0.0 Macrophages rest 0.1 Macrophages LPS 0.0 HUVEC none 7.3 HUVEC starved 17.7 HUVEC IL-1beta 4.8 HUVEC IFN gamma 14.7 HUVEC TNF alpha + IFN gamma 1.9 HUVEC TNF alpha + IL4 4.0 HUVEC IL-11 15.6 Lung Microvascular EC none 14.4 Lung Microvascular EC TNFalpha + IL-1beta 6.3 Microvascular Dermal EC none 15.4 Microsvasular Dermal EC TNFalpha + IL-1beta 5.1 Bronchial epithelium TNFalpha + IL1beta 2.6 Small airway epithelium none 0.8 Small airway epithelium TNFalpha + IL-1beta 3.4 Coronery artery SMC rest 0.1 Coronery artery SMC TNFalpha + IL-1beta 0.3 Astrocytes rest 3.6 Astrocytes TNFalpha + IL-1beta 6.9 KU-812 (Basophil) rest 0.0 KU-812 (Basophil) PMA/ionomycin 0.0 CCD1106 (Keratinocytes) none 0.3 CCD1106 (Keratinocytes) TNFalpha + IL-1beta 1.5 Liver cirrhosis 11.2 Lupus kidney 9.2 NCI-H292 none 20.2 NCI-H292 IL-4 17.4 NCI-H292 IL-9 21.6 NCI-H292 IL-13 9.5 NCI-H292 IFN gamma 10.3 HPAEC none 13.7 HPAEC TNF alpha + IL-1 beta 9.2 Lung fibroblast none 0.2 Lung fibroblast TNF alpha + IL-1 beta 0.8 Lung fibroblast IL-4 0.1 Lung fibroblast IL-9 0.2 Lung fibroblast IL-13 0.2 Lung fibroblast IFN gamma 0.3 Dermal fibroblast CCD1070 rest 0.1 Dermal fibroblast CCD1070 TNF alpha 0.0 Dermal fibroblast CCD1070 IL-1 beta 0.1 Dermal fibroblast IFN gamma 0.1 Dermal fibroblast IL-4 0.1 IBD Colitis 2 2.9 IBD Crohn's 9.2 Colon 100.0 Lung 19.3 Thymus 11.1 Kidney 6.4

[0670] CNS_neurodegeneration_v1.0 Summary: Ag6688 Expression of this gene is limited to a single sample from the parietal cortex (CT=34).

[0671] General_screening_panel_v1.6 Summary: Ag6688 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0672] Panel 1.3D Summary: Ag2000 Highest expression of this gene, a homolog of a transmembrane multi-pass protein, is seen in the cerebral cortex (CT=26.8), with moderate expression detectable across all regions of the brain. Because this gene shows a large down-regulation in brain cancers, its absence would be an excellent marker to determine if brain tissue was pre-cancerous in the examining and classifying of postmortem tissue

[0673] Expression of this gene is also widespread among tissues with metabolic relevance, including adipose, pancreas, adult and fetal heart, adult and fetal liver, adult and fetal skeletal muscle, and the adrenal, pituitary, and thyroid glands. The gene is expressed at much higher levels in fetal heart and skeletal muscle (CTs=28) than in adult heart and skeletal muscle (CTs=31-34). This differential expression pattern suggests that this gene expression could be used to differentiate between the two tissue sources for heart and skeletal muscle. Furthermore, the significantly higher level of expression of the gene in fetal skeletal muscle suggestes that this gene product may be involved in muscular growth or development in the fetus and could potentially act in a regenerative capacity in an adult. Therefore, therapeutic modulation of this gene could be useful in the treatment of muscle related diseases and the treatment of week or dystrophic muscle.

[0674] This gene is also expressed at significant levels in cell lines derived from ovarian, breast, lung, gastric, prostate and colon cancers compared to the normal tissues. Thus, the expression of this gene could be of use as a marker or as a therapeutic for ovarian, breast, lung, gastric, prostate and colon. In addition, therapeutic modulation of the product of this gene, through the use of peptides, chimeric molecules or small molecule drugs, may be useful in the treatment of these cancers.

[0675] Panel 2.2 Summary: Ag2000 Highest expression of this gene is seen in breast cancer (CT=28) as is seen in Panel 1.3D. In addition, there is significant overexpression of this gene in a cluster of breast, lung, and ovarian cancer samples when compared to corresponding normal tissues. Thus, expression of this gene could be used to differentiate breast, ovarian and lung cancers from normal tissue and as a marker for the presence of these cancers. Furthermore, therapeutic modulation of the protein product of this gene could be beneficial in the treatment of breast, ovarian and lung cancers. The expression of this gene also shows a reverse association with some normal stomach samples when compared to the matched gastric cancer tissue. This suggests that the this gene could be used to distinguish between normal and cancerous gastric tissue and that therapeutic modulation of the gene product may be useful in the treatment of gastric cancer.

[0676] Panel 4.1D Summary: Ag6688 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0677] Panel 4D Summary: Ag2000 The highest expression of this gene is found in the colon (CT=26.2), with modest expression detectable in the muco-epidremoid cell line H292, and the lung. It is also expressed at moderate levels on HUVEC and lung microvasculature regardless of their activation status. The protein encoded by this gene is homologous to an epidermal growth factor related protein (fibropellin like) and could be used as a marker of lung muco-epidermoid cells, colon or vasculature. The putative protein encoded by the transcript may also play an important role in the normal homeostasis of these tissues. Small molecule or antibody therapeutics designed with this gene product could be important for maintaining or restoring normal function to these organs during inflammation associated with asthma and emphysema.

[0678] K. CG58495-03 (NOV 17b): Pulmonary Surgactant-Associated Protein A Precursor.

[0679] Expression of gene CG58495-03 was assessed using the primer-probe set Ag7945, described in Table KA. TABLE KA Probe Name Ag7945 Start SEQ ID Primers Sequeces Length Position No Forward 5′-gcgtgcgaagtgaagga-3′ 17 135 159 Probe TET-5′-ctccaagccacactccacgacttcag-3′-TAMRA 26 153 160 Reverse 5′-ctgagggctccccttgtc-3′ 18 194 161

[0680] CNS_neurodegeneration_v1.0 Summary: Ag7945 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0681] Panel 4.1D Summary: Ag7945 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0682] L. CG97482-02 (NOV18b): S100 Calcium-Binding Protein-Like.

[0683] Expression of gene CG97482-02 was assessed using the primer-probe set Ag6384, described in Table LA. Results of the RTQ-PCR runs are shown in Table LB. Please note that CG97482-02 represents a fill length physical clone. TABLE LA Probe Name Ag6384 Start SEQ ID Primers Sequnces Length Position No Forward 5′-tggccctcatcgacgt-3′ 16 44 162 Probe TET-5′-agctcatcaacaatgagctttcccatt-3′-TAMRA 27 122 163 Reverse 5′-gcagtagtaaccacaacctcct-3′ 22 170 164

[0684] TABLE LB CNS_neurodegeneration_v1.0 Rel. Exp. (%) Ag6384, Run Tissue Name 269253944 AD 1 Hippo 28.3 AD 2 Hippo 92.7 AD 3 Hippo 4.2 AD 4 Hippo 17.7 AD 5 Hippo 36.1 AD 6 Hippo 100.0 Control 2 Hippo 82.9 Control 4 Hippo 65.1 Control (Path) 3 Hippo 13.7 AD 1 Temporal Ctx 22.4 AD 2 Temporal Ctx 74.7 AD 3 Temporal Ctx 4.7 AD 4 Temporal Ctx 42.0 AD 5 Inf Temporal Ctx 68.3 AD 5 Sup Temporal Ctx 75.8 AD 6 Inf Temporal Ctx 57.0 AD 6 Sup Temporal Ctx 45.4 Control 1 Temporal Ctx 21.8 Control 2 Temporal Ctx 56.3 Control 3 Temporal Ctx 35.4 Control 3 Temporal Ctx 30.6 Control (Path) 1 Temporal Ctx 42.0 Control (Path) 2 Temporal Ctx 39.8 Control (Path) 3 Temporal Ctx 5.1 Control (Path) 4 Temporal Ctx 25.9 AD 1 Occipital Ctx 19.5 AD 2 Occipital Ctx (Missing) 0.0 AD 3 Occipital Ctx 7.7 AD 4 Occipital Ctx 37.1 AD 5 Occipital Ctx 68.3 AD 6 Occipital Ctx 39.2 Control 1 Occipital Ctx 9.7 Control 2 Occipital Ctx 61.6 Control 3 Occipital Ctx 35.8 Control 4 Occipital Ctx 47.3 Control (Path) 1 Occipital Ctx 97.3 Control (Path) 2 Occipital Ctx 25.5 Control (Path) 3 Occipital Ctx 10.4 Control (Path) 4 Occipital Ctx 12.1 Control 1 Parietal Ctx 26.2 Control 2 Parietal Ctx 46.3 Control 3 Parietal Ctx 51.1 Control (Path) 1 Parietal Ctx 58.2 Control (Path) 2 Parietal Ctx 59.9 Control (Path) 3 Parietal Ctx 6.2 Control (Path) 4 Parietal Ctx 37.9

[0685] CNS_neurodegeneration_v1.0 Summary: Ag6384 No differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, this panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0686] Panel 4.1D Summary: Ag6384 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

Example D Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[0687] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.

[0688] SeqCalling assemblies produced by the exon linking process were selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted were selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences were analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.

[0689] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation's human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.

[0690] The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderborn et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).

[0691] Variants are reported individually but any combination of all or a select subset of variants are also included as contemplated NOVX embodiments of the invention.

[0692] NOV1b SNP Data (CG108030-02).

[0693] Seven polymorphic variants of NOV1b have been identified and are shown in Table 19A. TABLE 19A Variant of NOV1b. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13381876 354 T C 116 Leu Pro 13381877 627 T C 207 Leu Pro 13381845 2249 A C 0 N/A N/A 13381844 2454 C T 0 N/A N/A 13381881 2949 T C 0 N/A N/A 13381882 2959 A G 0 N/A N/A 13381883 3124 A G 0 N/A N/A

[0694] NOV2d SNP Data (CG115907-02).

[0695] Four polymorphic variants of NOV2d have been identified and are shown in Table 19B. TABLE 19B Variant of NOV2d. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13381868 204 T C 25 Thr Thr 13381869 1892 T A 588 Leu His 13381842 2131 C A 668 Pro Thr 13381871 2544 G A 805 Leu Leu

[0696] NOV6a SNP Data (CG155653-01).

[0697] Three polymorphic variants of NOV6a have been identified and are shown in Table 19C. TABLE 19C Variant of NOV6a. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13381864 301 G A 42 Gly Ser 13381889 1260 G T 361 Arg Ser 13381867 4013 G A 0 N/A N/A

[0698] NOV7a SNP Data (CG160093-01).

[0699] Three polymorphic variants of NOV7a have been identified and are shown in Table 19D. TABLE 19D Variant of NOV7a. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13381888 966 A G 315 Glu Gly 13381887 980 A G 320 Thr Ala 13381886 1008 T C 329 Leu Ser

[0700] NOV9a SNP Data (CG165528-01).

[0701] Four polymorphic variants of NOV9a have been identified and are shown in Table 19E. TABLE 19E Variant of NOV9a. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13381837 78 C T 0 N/A N/A 13381838 4640 T C 1514 Val Ala 13381839 4754 A G 0 N/A N/A 13381840 4936 A G 0 N/A N/A

[0702] NOV12d SNP Data (CG165719-01).

[0703] Four polymorphic variants of NOV12d have been identified and are shown in Table 19F. TABLE 19F Variant of NOV12d. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13381873 291 C A 77 Ser Ser 13381875 475 T C 139 Phe Leu 13381874 559 G A 167 Ala Thr 13381884 631 T C 191 Phe Leu

[0704] NOV17b SNP Data (CG58495-03).

[0705] Three polymorphic variants of NOV17b have been identified and are shown in Table 19G. TABLE 19G Variant of NOV17b. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13376633 151 A G 24 Glu Gly 13381911 386 T C 102 Tyr Tyr 13376634 501 A C 141 Lys Gln

[0706] NOV18b SNP Data (CG97482-02).

[0707] One polymorphic variant of NOV18b has been identified and is shown in Table 19H. TABLE 19H Variant of NOV18b. Nucleotides Amino Acids Variant Position Initial Modified Position Initial Modified 13376808 176 T C 53 Val Ala

Example E CG50970-01, NOV15b

[0708] Role in inflammation: This transcript encodes glypican 2 a glycosylphosphatidylinositol (gpi) achored cell surface heparan sulfate proteoglycan. This type of proteoglycan can bind cytokines and is potentially involved in lymphocytic migration and activation (1). Additionally, this molecule is also found in bone marrow and cartilage (2-3) and may be involved in osteoblast function and hematopoiesis.

[0709] Therapeutic function: Antibody therapeutics which antagonized the function of the protein encoded for by this transcript could be used to reduce or inhibit lymphocyte extravasation associated with inflammation due to asthma, emphysema, rheumatoid arthritis, IBD or psoriasis. Antibodies may also block tissue changes associated with osteoarthritis (4).

Example E1 Gene Expression Analysis Using CuraChip in Human Tissues from Tumors and from Equivalent Normal Tissues

[0710] CuraGen has developed a gene microarray (CuraChip 1.2) for target identification. It provides a high-throughput means of global mRNA expression analyses of CuraGen's collection of cDNA sequences representing the Pharmaceutically Tractable Genome (PTG). This sequence set includes genes which can be developed into protein therapeutics, or used to develop antibody or small molecule therapeutics. CuraChip 1.2 contains 11,000 oligos representing approximately 8,500 gene loci, including (but not restricted to) kinases, ion channels, G-protein coupled receptors (GPCRs), nuclear hormone receptors, proteases, transporters, metabolic enzymes, hormones, growth factors, chemokines, cytokines, complement and coagulation factors, and cell surface receptors.

[0711] The CuraChip cDNAs were represented as 30-mer oligodeoxyribonucleotides (oligos) on a glass microchip. Hybridization methods using the longer CuraChip oligos are more specific compared to methods using 25-mer oligos. CuraChip oligos were synthesized with a linker, purified to remove truncated oligos (which can influence hybridization strength and specificity), and spotted on a glass slide. Oligo-dT primers were used to generate cRNA probes for hybridization from samples of interest. A biotin-avidin conjugation system was used to detect hybridized probes with a fluorophore-labeled secondary antibody. Gene expression was analyzed using clustering and correlation bioinformatics tools such as Spotfire® (Spotfire, Inc., 212 Elm Street, Somerville, Mass. 02144) and statistical tools such as multivariate analysis (MVA).

[0712] Results of PTG Chip 1.2: One hundred seventy-eight samples of RNA from tissues obtained from surgically dissected tumors, non-diseased tissues from the corresponding organs and tumor xenografts grown in nude nu/nu mices were used to generate probes and run on PTG Chip 1.2. An oligo (optg2_(—)0011299) that corresponds to CG50970 on the PTG Chip 1.2 was scrutinized for its expression profile. The statistical analysis identify significant over-expression in a subset of lung tumors, about 30%, compared with corresponding normal lung tissue and strong expression in breast cancers, also about 30%, which do not have matched normal tissue. It is also useful that the expression of this gene is mantained when human tumor cell lines are grown as tumor xenografts in nude mice, especially by the lung tumor cell lines NCI-H82 and NCI-H69. Therfore these tumor xenografts can be used as animal models.

[0713] Thus, based upon its profile, the expression of this gene could be of use as a marker for subsets of lung and breast cancers. In addition, therapeutic inhibition of the activity of the product of this gene, through the use of antibodies or small molecule drugs, may be useful in the therapy of lung and breast cancers that express CG50970.

Example E2 Protein Expression and Purification

[0714] CG50970-05 is expressed and purified in the CHO stable cell system using the Wave bioreactor.

[0715] To separate the glycanated form of the proteoglycan from the unglycanated core protein, the conditioned medium was applied to a 0.9×8-cm column of DEAE-Sephacel equilibrated with 150 mM NaCl, 50 mM Tris-HCl, pH 8.0. After elution with 50 mM Tris-HCl (pH 8.0) containing 0.6 M NaCl, the glycanated glypican-1-Fc was bound to protein A-Sepharose beads and eluted with 0.1 M glycine, pH 3.0.

[0716] Procedure

[0717] 1. Transfected into attached CHO stable cells with Lipofectamine 2000 in Opti-MEM 1. Overlay with DMEM media with 5% FBS after 4 hours.

[0718] 2. Harvested after 3, 5 and 7 days incubation at 37° C.

[0719] Cell Lysis/Protein Recovery

[0720] Procedure

[0721] 1. Centrifuged at 3000 rpm for 10 min and filter with 0.2 um pore size.

[0722] Procedure

[0723] 1. Metal Affinity Chromatography—Pharmacia 50 nm and 5 ml Metal Chelate—Running buffer 20 mM phosphate, pH 7.4, 0.5 M NaCl. Wash with 20 mM, 50 mM, and 100 mM Imidazole. Elute with 500 mM Imidazole.

[0724] 2. HS Cation Exchange Chromatography-Poros HS 1.6 ml column-30 mM Tris-Cl, pH 8.0, 0.05% CHAPS. Elute with 0-2 M NaCl gradient.

[0725] 3. Dialysis—@ 4° C. using 3,500 MWCO against 20 mM Tris-HCl, pH 7.4+150 mM NaCl.

[0726] Protein Quality Control

[0727] Western Blot Procedure

[0728] Antibody name, catalog # and supplier: Anti-V5-HRP Antibody, 46-0708, Invitrogen (Carlsbad, Calif.), S-protein HRP conjugate, 69047. Novagen (Madison, Wis.)

[0729] Antibody dilution buffer: PBS/5% milk/0.1% Tween-20

[0730] Wash buffer: PBS/0.1% Tween-20

[0731] Detection reagents: ECL (Amersham Biosciences Corp., Piscataway, N.J.)

[0732] 1. The blot was covered with antibody dilution buffer and incubated on a rocker for one hour at room temperature.

[0733] 2. The blocking solution was replaced with antibody dilution buffer containing the appropriate amount of conjugate, and the blot was incubated on a rocking platform for one hour at room temperature.

[0734] 3. The antibody solution was decanted, and the blot was washed quickly with two quick rinses of wash buffer. The blot was then covered with wash buffer and incubated on the rocking platform for five minutes, and the wash buffer was decanted. This process was repeated twice for a total of three five-minute washes.

[0735] 4. The blot was developed using ECL reagents (Amersham Biosciences Corp., Piscataway, N.J.) as per manufacturer instructons and luminescence was then digitized on a Kodak Image Sciences Imaging Station.

[0736] Expression of CG50970-05 in Stable CHO-K1 Cells.

[0737] A 1590 bp long BamHI-XhoI fragment containing the CG50970-05 sequence was subcloned into BamHI-XhoI digested pEE14.4Sec2 and pEE14.4SecFc3. The resulting plasmids are transfected into CHO-K1 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Invitrogen/Gibco). The cell pellet and supernatant are harvested 72 h post transfection and examined for CG50970-05 expression by Western blot (reducing conditions) using an anti-V5 antibody.

[0738] MSX resistant clones are selected using the GS system (Lonza Biologicals) The culture media in the selection process was: Glutamin-free DMEM (JRH), 10% dialyzed FBS, 1×GS supplement (JRH), 25 uM MSX (JRH).

[0739] A high expressor clone, is selected for scale up in 10 LWave bioreactors. Two reactors were inoculated. 30 L conditioned media was collected from each reactors yielding batches 2 and 3.

[0740] The culture media was harvested 120 h after inoculating the Wave bioreactor and examined for CG50970-05 expression by Western blot (reducing conditions) using an anti-V5 antibody

Example E3 Growth Factor Mediated Proliferation Assays

[0741] Several growth factors require the presence of heparan sulfate for high affinity binding to their tyrosine kinase receptors and therefore use HSPG's as coreceptors in their signaling. We determine whether it is possible to modulate responsiveness to heparin-binding growth factors by altering CG50970 protein levels, either increasing them or decreasing them. Kleeff et al (J. Clin. Invest. Volume 102, Number 9, November 1998, 1662-1673) and Matsuda et al (Cancer Research 61, 5562-5569, Jul. 15, 2001) used this approach to demonstrate the activity of Glypican-1.

[0742] Tumor cell lines with low level of CG50970 are transiently transfected with mature forms of CG50970, variants 06 and 07. The increase in expression of CG50970 is then monitored by western blot analysis. Next, the effects of growth factors on cell growth are determined during the 48-96 h interval after transfection, when CG50970 protein levels are maximally increased. Cells are treated with several growth factors like FGF2, HB-EGF. Cells expressing CG50970 will have a higher rate of proliferation in response to the growth factors than control cells.

[0743] Tumor cell lines with high level of CG50970 are transiently transfected with antisense oligos directed against CG50970. The decrease in expression of CG50970 is then monitored by PCR-based methods. Next, the effects of growth factors on cell growth are determined during the 48-96 h interval after transfection, when CG50970 protein levels are maximally decrease. Cells are treated with Fetal Bovine Serum or individual growth factors like FGF2, HB-EGF. As shown in table E3a below, cells treated with CG50970 antisense 1 and stimulated with with Fetal Bovine Serum have a lower rate of proliferation in response to the growth factors than control cells.

[0744] Sequences of the antisense oligos, relative position and length that correspond to Table E3a. AS1 ATGTCCGCGCTGCGACCTCT 1 20 0.0 AS2 ATGTCCGCGCTGCGACCTCT 1 20 0.0 AS3 CCGGAGCGAGGCAAAGGTCA 66 20 0.0 AS4 AACGACCGCCGCAGGCACCA 1137 20 0.0 AS5 GCTTGGACCTCGATAACGGG 1725 20 0.0

Example E4 Preparation of Antibodies that Bind CG50970

[0745] As described above, inhibiting CG50970 activity has utility in cancer therapy and specifically in inhibiting lung and breast cancers. It is know in the art that antibodies that bind HSPGs factors like CG50970 can inhibit their activity in a process called neutralization. Specifically, neutralizing monoclonal antibodies that bind syndecan-3 interfered with FGF-2 mitogenic action, but not that of insulin-like growth factor-1 or parathyroid hormone (Kirsch et al. J Biol Chem, Nov. 1, 2002;277(44):42171-7). Therefore production of polyclonal and monoclonal antibodies directed against CG57094 has utility in cancer therapy and specifically in inhibiting kidney, lung, melanomas and breast cancers. As opposed to VEGF, that is needed only for tumor induced endothelial cell growth and survival, CG57094 is required for cell growth and survival both by endothelial and tumor cells, therefore inhibition of CG57094 activity could have a more pronounced therapeutic effect.

[0746] Method: Techniques for producing the antibodies are known in the art and are described, for example, in “Antibodies, a Laboratory Manual” Eds Harlow and Lane, Cold Spring Harbor publisher. Both rabbits and mice are suitable for the production of polyclonal antibodies, while mice are also suitable for the production of monoclonal antibodies. Mice where the human immunoglubolin genes have replaced the mouse immunoglubolin genes can be used to produce fully human monoclonal antibodies. These antibodies have better pharmaceutical characteristic, no or minimal antibody directed immune reactions that results in loss of therapeutic efficacy and have been shown to eradicate tumor in animal model (Yang X D, Jia X C, Corvalan J R, Wang P, Davis C G, Jakobovits A Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res Mar. 15, 1999;59(6):1236-43).

[0747] Generation of Rabbit Polyclonal Antibodies

[0748] Rabbit are immunized with the immunogen emulsified in complete Freund's adjuvant and injected subcutaneously or intraperitoneally or intramuscolar in an amount from 50-1000 micrograms. The immunized rabbits are then boosted 10 to 12 days later with additional immunogen emulsified in the selected adjuvant. Thereafter, for several weeks, the rabbits might also be boosted with additional immunization injections. Serum samples may be periodically obtained from the rabbit by bleeding of the ear for testing ELISA assays to detect the antibodies.

[0749] Generation of Human Monoclonal Antibodies

[0750] Fully human monoclonal antibodies (MAb), direct against CG50970-05 are generated from human antibody-producing XenoMouse strains engineered to be deficient in mouse antibody production and to contain the majority of the human antibody gene repertoire on megabase-sized fragments from the human heavy and kappa light chain loci as previously described in Yang et al. (Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res Mar. 15, 1999;59(6):1236-43).

[0751] Elisa assay is then used to determine the specificity of the antibodies.

Example E5 ELISA Protocol to Determine Binding of the Antibodies

[0752] Solution Preparation

[0753] Coating Buffer (0.1M Carbonate, pH9.5)

[0754] 8.4 g. NaHCO3, 3.56 g. Na2CO3, pH to 9.5, and dilute to 1 L. with ddH2O

Assay Diluent

[0755] Pharmingen #26411E

Protocol

[0756] Coat a 96-well high protein binding ELISA plate (Corning Costar #3590) with 50 ul. of protein at a concentration of 5 ug/mL. in coating buffer overnight at 4 degrees.

[0757] Following day wash the cells 5×200-300 ul. of 0.5% Tween-20 in PBS.

[0758] Block plates with 200 ul. of assay diluent for at least 1 hour at room temperature.

[0759] Dilute antibodies in assay diluent.

[0760] Wash plate as in step 2.

[0761] Add 50 ul. of each antibody dilution to the proper wells for at least 2 hours at room temp.

[0762] Wash plate as in step 2.

[0763] Add 50 ul. of secondary antibody and incubate for 1 hour at room temp.

[0764] Wash plate as in step 2.

[0765] Develop assay with 100 ul. of TMB substrate solution/well. (1:1 ratio of solution A+B) (Pharmingen #2642KK)

[0766] Stop reaction with 50 ul. sulfuric acid

[0767] Read plate at 450 nm with a correction of 550 nm.

Example 6 Identification of CG50970 Neutralizing Antibodies

[0768] As mentioned above, proteoglycans like CG50970 have affinity for glycosaminoglycan (GAG)-binding proteins like laminin-1 and midkine. Specifically, Herndon et al (Glycobiology 1999 February;9(2):143-55) have previously shown that rat glypican-2 has an high affinity for laminin-1, while Kurosawa et al. (Glycoconj J 2001 June;18(6):499-507) have shown that rat glypican-2 has an high affinity for midkine.

[0769] As previously discussed, the identification of antibodies, preferably fully human monoclonal antibodies that bind to CG50970 and neutralize its activity, limiting or abolishing its ability to bind to glycosaminoglycan (GAG)-binding proteins like laminin-1 and midkine, would be very beneficial because these antibodies will have therapeutic effect against tumors, specifically against lung and breast cancers. To determine whether an antibody can neutralize CG50970 activity, various amounts of such antibody are added to the Receptor-ligand Elisa assay as described in the method below.

[0770] Receptor-ligand Elisa assay Protocol—96-well plates (Corning Costar, catalog no. 9018) are coated overnight with the laminin-1 (BT-276 from BTI website at btiinc.com/page/catal.html#Laminin) or midkine (258-MD from R&D system) at a saturating concentration of in phosphate-buffered saline. After removing the unbound protein by washing with TBST (10 mM Tris-HCl, pH 7.4, 150 mM NaCl, 0.1% Tween 20), the wells were blocked with 10% fetal bovine serum in TBST for 2 h and then incubated for 18 h at room temperature with varying concentrations of glycanated CG50970-05-Fc in phosphate-buffered saline in the presence or absence of various amounts of monoclonal antibodies that bind to CG50970. The CG50970-05-Fc bound to laminin-1 proteins was detected using a biotinylated anti-human Fc antibody (Jackson ImmunoResearch Laboratories, Inc.; 1:250,000 in TBST, for 2 h) followed by incubation for 20 min with horseradish peroxidase-conjugated streptavidin (1:20,000 in TBST). The colorimetric reaction product from the o-phenylenediamine substrate was measured at 450 nm using a Dynatech MRX ELISA plate reader. Nonspecific binding was calculated as the binding of glypican-2-Fc to wells coated with 100 μg of bovine serum albumin.

[0771] Antibodies identified with this assay are then tested at various concentrations in the growth factor mediated proliferation assay described in example 4 to determine whether they can inhibit cellular proliferation.

[0772] Antibody that can neutralize the CG50970-05-Fc biochemical activity and have anti-proliferative activity can be useful as therapeutic agents.

Example 7 Quantification of Membrane Bound CG50970 by Flow Cytometry

[0773] CG50970 is a type 1 membrane protein, therefore Mabs binding to this protein could be able to stain the membrane of cells expressing CG50970 in a Flow Cytometry assay (FACS). It is known in the art that not all antibodies that recognize a recombinant protein in Elisa or IHC assays will also work in FACS. At the same time those antibodies that do are preferred because they have a higher chance to recognize the antigen in-vivo in patients and therefore have a potential use as therapeutic or ex-vivo diagnostic agents. We therefore set-up a FACS assay using cell lines that express CG50970, like lung ca.ncer NCI-H146, NCI-H526 or breast cancer BT 549 and one that express it at much lower level, lung ca.ncer HOP-62 and breast cancer T47D.

[0774] Flow Cytometry Protocol for Adherent Cells (ver.1) 11-25-02 KT

[0775] 1. Wash cells with 1×PBS (Ca and Mg free) twice.

[0776] 2. Add Versene and incubate at 37° C. until the cells detach.

[0777] 3. Count cells. Use <1 million cells per assay tube.

[0778] 4. Wash the cells twice with ice-cold FACS buffer.

[0779] 5. Resuspend cells in 100 ul of ice-cold FACS buffer. Mix.

[0780] 6. Add primary mAb. Incubate on ice for 30 min.

[0781] 7. Wash cells 2-3 times with 1 ml of ice-cold FACS buffer.

[0782] 8. Resuspend cells in 100 ul ice-cold FACS buffer. Mix.

[0783] 9. Add secondary (conjugated) mAb. Incubate on ice for 30 min with a cover.

[0784] 10. Wash cells 2-3 times with 1 ml of ice-cold FACS buffer.

[0785] 11. Fix cells with 0.5-1 ml of 1% formaldehyde (in PBS) and analyze by Flow Cytometry.

[0786] FACS Buffer: 0.01 M HEPES (pH 7.4) 0.15 M NaCl --------------------- (may be substituted by PBS) 0.1%   NaN₃  4%  FBS

Example 8 Preparing and Testing of Chemotherapy and Radioimmunoconjugated Antibodies

[0787] Cytotoxic chemotherapy or radiotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. There therefore the need to improve the selectivity. One strategy is to couple the therapeutics to antibodies that recognize tumour-associated antigens. This increases the exposure of the malignant cells, and reduces the exposure of normal cells, to the ligand-targeted therapeutics (reviewed in Allen Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2002 October;2(10):750-63)

[0788] CG56972-03 is one of these tumour-associated antigen, as shown by its specific expression on cellular membranes of tumor cells by FACS and IHC.

[0789] Therefore the fully human monoclonal antibodies direct against CG50970-05 disclosed in this application could be coupled to cytotoxic chemotherapic agents or radiotherapic agents to generate anti-tumor therapeutics.

[0790] Depending on the intended use of the antibody, i.e., as a diagnostic or therapeutic reagent, radiolabels are known in the art and have been used for similar purposes. For instance, radionuclides which have been used in clinical diagnosis include .sup.131 I, .sup.125 I, .sup.123 I, .sup.99 Tc, .sup.67 Ga, as well as .sup.111 In. Antibodies have also been labeled with a variety of radionuclides for potential use in targeted immunotherapy (Peirersz et al. (1987) The use of monoclonal antibody conjugates for the diagnosis and treatment of cancer. Immunol. Cell Biol65: 111-125). These radionuclides include .sup.188 Re and .sup.186 Re as well as .sup.90 Y, and to a lesser extent .sup.199 Au and .sup.67 Cu. 1-(131) has also been used for therapeutic purposes. U.S. Pat. No. 5,460,785 provides a listing of such radioisotopes and is herein incorporated by reference.

[0791] Patents relating to radiotherapeutic chelators and chelator conjugates are known in the art. For instance, U.S. Pat. No. 4,831,175 of Gansow is directed to polysubstituted diethylenetriaminepentaacetic acid chelates and protein conjugates containing the same, and methods for their preparation. U.S. Pat. Nos. 5,099,069, 5,246,692, 5,286,850, and 5,124,471 of Gansow also relate to polysubstituted DTPA chelates. These patents are incorporated herein in their entirety.

[0792] Cytotoxic chemotherapy are known in the art and have been used for similar purposes. For instance, U.S. Pat. No 6,441,163 describes the process for the production of cytotoxic conjugates of maytansinoids and antibodies. The anti-tumro activity of a new tubulin polymerization inhibitor, auristatin PE, is know in the art (Mohammad et al. Int J Oncol 1999 August;15(2):367-72).

[0793] Once these conjugates of chemotherapy or radiolabels and antibodies is made, it is tested for its cytotoxic activity on CG50970-05 positive cells, using methods know in the art like by MTS, Cell counts and clonogenic assays.

[0794] Other Embodiments

[0795] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.

1 169 1 2566 DNA Homo sapiens CDS (288)..(1454) misc_feature (3)..(3) Wherein n may be a, c, g or t 1 ggncacgagc ggccctccac tccctgactg tcgtgtttgt ctcgctctgt gctgagggct 60 gatgctgagg acctccttga ctccttcctt agcaacattc tacaggactg caggcaccac 120 ctgtgtgaac cggacatgaa actggtgtgg cctagtgcca agctgttgca ggcagctgca 180 ggtgcatctg cccgggcctg tgactctgtc accagcaagt actgccttta ctgctggaac 240 agttccacaa gcacagtcag agcagccagc ggcggacaat ccttgaa atg ctc ctg 296 Met Leu Leu 1 ggt ttc ttg aag ctg cag cag aaa tgg agc tat gaa gac aaa gat caa 344 Gly Phe Leu Lys Leu Gln Gln Lys Trp Ser Tyr Glu Asp Lys Asp Gln 5 10 15 agg cct ctg aat ggc ttc aag gac cag ctg tgc tca ctg gta ttc atg 392 Arg Pro Leu Asn Gly Phe Lys Asp Gln Leu Cys Ser Leu Val Phe Met 20 25 30 35 gct cta aca gac ccc agc acc cag ctt cag ctt gtt ggc atc cgt aca 440 Ala Leu Thr Asp Pro Ser Thr Gln Leu Gln Leu Val Gly Ile Arg Thr 40 45 50 ctg aca gtc ttg ggt gcc cag cca gat ctc cta tct tat gag gac ttg 488 Leu Thr Val Leu Gly Ala Gln Pro Asp Leu Leu Ser Tyr Glu Asp Leu 55 60 65 gag ctg gca gtg ggt cac ctg tac aga ctg agc ttc ctg aag gag gat 536 Glu Leu Ala Val Gly His Leu Tyr Arg Leu Ser Phe Leu Lys Glu Asp 70 75 80 tcc cag agt tgc agg gtg gca gca ctg gaa gca tca gga acc ctg gct 584 Ser Gln Ser Cys Arg Val Ala Ala Leu Glu Ala Ser Gly Thr Leu Ala 85 90 95 gct ctc tac cct gtg gcc ttc agc agc cac ctc gta ccc aag ctc gct 632 Ala Leu Tyr Pro Val Ala Phe Ser Ser His Leu Val Pro Lys Leu Ala 100 105 110 115 gag gag ctg cgt gta ggg gag tca aat ttg act aac gga gat gag ccc 680 Glu Glu Leu Arg Val Gly Glu Ser Asn Leu Thr Asn Gly Asp Glu Pro 120 125 130 acc caa tgc tcc cgg cat ctg tgc tgt ctg caa gcc ttg tca gct gta 728 Thr Gln Cys Ser Arg His Leu Cys Cys Leu Gln Ala Leu Ser Ala Val 135 140 145 tca aca cat ccc agc atc gtc aag gag aca ctg cct ctg ctg ctg cag 776 Ser Thr His Pro Ser Ile Val Lys Glu Thr Leu Pro Leu Leu Leu Gln 150 155 160 cat ctc tgg caa gtg aac aga ggg aat atg gtt gca caa tcc agt gac 824 His Leu Trp Gln Val Asn Arg Gly Asn Met Val Ala Gln Ser Ser Asp 165 170 175 gtt att gct gtc tgt cag agc ctc aga cag atg gca gaa aaa tgt cag 872 Val Ile Ala Val Cys Gln Ser Leu Arg Gln Met Ala Glu Lys Cys Gln 180 185 190 195 cag gac cct gag agt tgc tgg tat ttc cac cag aca gct ata cct tgc 920 Gln Asp Pro Glu Ser Cys Trp Tyr Phe His Gln Thr Ala Ile Pro Cys 200 205 210 ctg ctt gcc ttg gct gtg cag gcc tct atg cca gag aag gag ccc tca 968 Leu Leu Ala Leu Ala Val Gln Ala Ser Met Pro Glu Lys Glu Pro Ser 215 220 225 gtt ctg aga aaa gta cta ttg gag gat gag gtg ttg gct gcc atg gtg 1016 Val Leu Arg Lys Val Leu Leu Glu Asp Glu Val Leu Ala Ala Met Val 230 235 240 tct gtc att ggc act gct aca acc cac ctg agc cct gag tta gct gcc 1064 Ser Val Ile Gly Thr Ala Thr Thr His Leu Ser Pro Glu Leu Ala Ala 245 250 255 cag agt gtg aca cac att gtg ccc ctc ttc ttg gat ggc aac gtg tcc 1112 Gln Ser Val Thr His Ile Val Pro Leu Phe Leu Asp Gly Asn Val Ser 260 265 270 275 ttt ctg cct gaa aac agc ttc ccg agc aga ttc cag cca ttc cag gat 1160 Phe Leu Pro Glu Asn Ser Phe Pro Ser Arg Phe Gln Pro Phe Gln Asp 280 285 290 ggc tcc tca ggg cag agg cgg ctg att gca ctg ctt atg gcc ttt gtc 1208 Gly Ser Ser Gly Gln Arg Arg Leu Ile Ala Leu Leu Met Ala Phe Val 295 300 305 tgc tcc ctg cct cga aat gtg gaa atc cct cag ctg aac caa ctc atg 1256 Cys Ser Leu Pro Arg Asn Val Glu Ile Pro Gln Leu Asn Gln Leu Met 310 315 320 cgg gag ctt ttg gaa ctg agc tgc tgc cac agc tgc ccc ttt tct tcc 1304 Arg Glu Leu Leu Glu Leu Ser Cys Cys His Ser Cys Pro Phe Ser Ser 325 330 335 acc gct gct gcc aag tgc ttt gca gga ctc ctc aac aag cac cct gca 1352 Thr Ala Ala Ala Lys Cys Phe Ala Gly Leu Leu Asn Lys His Pro Ala 340 345 350 355 ggg cag cag ctg gat gaa ttc cta cag cta gct gtg gac aaa gtg gag 1400 Gly Gln Gln Leu Asp Glu Phe Leu Gln Leu Ala Val Asp Lys Val Glu 360 365 370 gct ggc ctg gct ctg ggc cct gtc gta gtc agg cct tca ctc ttc ttc 1448 Ala Gly Leu Ala Leu Gly Pro Val Val Val Arg Pro Ser Leu Phe Phe 375 380 385 tct ggg taacaaaggc cctagtgctc agataccatc ctctcagctc ctgccttaca 1504 Ser Gly gcccggctca tgggcctcct gagtgaccca gaattaggtc cagcagcagc tgatggcttc 1564 tctctgctca tgtctgactg cactgatgtg ctgactcgtg ctggccatgc cgaagtgcgg 1624 atcatgttcc gccagcggtt cttcacagat aatgtgcctg ctttggtcca gggcttccat 1684 gctgctcccc aagatgtgaa gccaaactac ttgaagggtc tttctcatgt acttaacagg 1744 ctgcccaagc ctgactcttg ccagagctgc ccacgcttct ttccttgctg ctggaggccc 1804 tgtcctgccc tgactgtgtg gtgcagctct ccaccctcag ctgccttcag cctcttctac 1864 tggaagcacc ccaagtcatg agtcttcacg tggacaccct cgtcaccaag tttctgaacc 1924 tcagctctag cccttccatg gctgtccgga tcgccgcact gcagtgcatg catgctctca 1984 ctcgcctgcc cacccctgtg ctgctgccgt acaaaccaca ggtgattcgg gccttagcca 2044 aacccctgga tgacaagaag agactggtgc gcaaggaagc agtgtcagcc agaggggagt 2104 ggtttctgtt ggggagccct ggcagctgag ccctcagtcc tggcctagac tgttctgaca 2164 atctaacctg ggattactaa ctgttgagcc atcttcccca aagcagggaa accactggtc 2224 tctgactgcc tttcccacag acacagcaca aatgctaggc ctctgttgca tggctgtaca 2284 aagaacataa gagtccatat ttctagtgga tttgtaaaat aagtgtgtgt gagacacttg 2344 cgtttgaaga aagatctagg gtcctgggtc tcttgcattt atatgtcaga aaaggggcga 2404 tatgctgctg aggggtgagt gcatatgagt gtggccctga ggaccagggc tggcagatgt 2464 tgtctacctg ctgaagaata aagatttctt ttggtaaaaa aaaaaaaaaa gggcggccgc 2524 tctagaggat ccctcgaggg gcgcaagctt acgcgancan gc 2566 2 389 PRT Homo sapiens 2 Met Leu Leu Gly Phe Leu Lys Leu Gln Gln Lys Trp Ser Tyr Glu Asp 1 5 10 15 Lys Asp Gln Arg Pro Leu Asn Gly Phe Lys Asp Gln Leu Cys Ser Leu 20 25 30 Val Phe Met Ala Leu Thr Asp Pro Ser Thr Gln Leu Gln Leu Val Gly 35 40 45 Ile Arg Thr Leu Thr Val Leu Gly Ala Gln Pro Asp Leu Leu Ser Tyr 50 55 60 Glu Asp Leu Glu Leu Ala Val Gly His Leu Tyr Arg Leu Ser Phe Leu 65 70 75 80 Lys Glu Asp Ser Gln Ser Cys Arg Val Ala Ala Leu Glu Ala Ser Gly 85 90 95 Thr Leu Ala Ala Leu Tyr Pro Val Ala Phe Ser Ser His Leu Val Pro 100 105 110 Lys Leu Ala Glu Glu Leu Arg Val Gly Glu Ser Asn Leu Thr Asn Gly 115 120 125 Asp Glu Pro Thr Gln Cys Ser Arg His Leu Cys Cys Leu Gln Ala Leu 130 135 140 Ser Ala Val Ser Thr His Pro Ser Ile Val Lys Glu Thr Leu Pro Leu 145 150 155 160 Leu Leu Gln His Leu Trp Gln Val Asn Arg Gly Asn Met Val Ala Gln 165 170 175 Ser Ser Asp Val Ile Ala Val Cys Gln Ser Leu Arg Gln Met Ala Glu 180 185 190 Lys Cys Gln Gln Asp Pro Glu Ser Cys Trp Tyr Phe His Gln Thr Ala 195 200 205 Ile Pro Cys Leu Leu Ala Leu Ala Val Gln Ala Ser Met Pro Glu Lys 210 215 220 Glu Pro Ser Val Leu Arg Lys Val Leu Leu Glu Asp Glu Val Leu Ala 225 230 235 240 Ala Met Val Ser Val Ile Gly Thr Ala Thr Thr His Leu Ser Pro Glu 245 250 255 Leu Ala Ala Gln Ser Val Thr His Ile Val Pro Leu Phe Leu Asp Gly 260 265 270 Asn Val Ser Phe Leu Pro Glu Asn Ser Phe Pro Ser Arg Phe Gln Pro 275 280 285 Phe Gln Asp Gly Ser Ser Gly Gln Arg Arg Leu Ile Ala Leu Leu Met 290 295 300 Ala Phe Val Cys Ser Leu Pro Arg Asn Val Glu Ile Pro Gln Leu Asn 305 310 315 320 Gln Leu Met Arg Glu Leu Leu Glu Leu Ser Cys Cys His Ser Cys Pro 325 330 335 Phe Ser Ser Thr Ala Ala Ala Lys Cys Phe Ala Gly Leu Leu Asn Lys 340 345 350 His Pro Ala Gly Gln Gln Leu Asp Glu Phe Leu Gln Leu Ala Val Asp 355 360 365 Lys Val Glu Ala Gly Leu Ala Leu Gly Pro Val Val Val Arg Pro Ser 370 375 380 Leu Phe Phe Ser Gly 385 3 3319 DNA Homo sapiens CDS (8)..(2218) 3 tcgcgtt atg gcc gct gcc gcg gct gtg gag gcg gcg gcg cct atg ggt 49 Met Ala Ala Ala Ala Ala Val Glu Ala Ala Ala Pro Met Gly 1 5 10 gcc cta tgg ggc ctc gtg cac gac ttc gtc gtg ggt cag caa gag ggc 97 Ala Leu Trp Gly Leu Val His Asp Phe Val Val Gly Gln Gln Glu Gly 15 20 25 30 ccc gct gac cag gtg gct gca gat gtg aaa tct ggc aac tat aca gtg 145 Pro Ala Asp Gln Val Ala Ala Asp Val Lys Ser Gly Asn Tyr Thr Val 35 40 45 tta caa gtt gtg gaa gcc ctt ggg tcc tct cta gag aat cca gaa ccc 193 Leu Gln Val Val Glu Ala Leu Gly Ser Ser Leu Glu Asn Pro Glu Pro 50 55 60 cga act cgg gca cga gga atc cag ctt ttg tca cag gtg cta ctc cac 241 Arg Thr Arg Ala Arg Gly Ile Gln Leu Leu Ser Gln Val Leu Leu His 65 70 75 tgt cac acc ttg ctc ctg gag aag gaa gtg gta cac ctg ata ctg ttc 289 Cys His Thr Leu Leu Leu Glu Lys Glu Val Val His Leu Ile Leu Phe 80 85 90 tat gag aac cgg ctg aag gac cat cat ctt gtg atc cca tct gtc ctg 337 Tyr Glu Asn Arg Leu Lys Asp His His Leu Val Ile Pro Ser Val Leu 95 100 105 110 cag ggt ttg aag gca ctt agc ctg tgt gtg gcc ctg ccc cca ggg ctg 385 Gln Gly Leu Lys Ala Leu Ser Leu Cys Val Ala Leu Pro Pro Gly Leu 115 120 125 gct gtt tct gtg ctt aaa gcc atc ttc cag gaa gtg cat gta cag tcc 433 Ala Val Ser Val Leu Lys Ala Ile Phe Gln Glu Val His Val Gln Ser 130 135 140 ctg cca cag gtg gac cga cac aca gtc tac aat atc atc acc aat ttt 481 Leu Pro Gln Val Asp Arg His Thr Val Tyr Asn Ile Ile Thr Asn Phe 145 150 155 atg cga acc cgg gaa gaa gag cta aag agc cta gga gct gac ttc acc 529 Met Arg Thr Arg Glu Glu Glu Leu Lys Ser Leu Gly Ala Asp Phe Thr 160 165 170 ttt ggc ttc atc cag gtg atg gat ggg gaa aag gat ccc cgt aat ctt 577 Phe Gly Phe Ile Gln Val Met Asp Gly Glu Lys Asp Pro Arg Asn Leu 175 180 185 190 ctg gtg gcc ttc cgc atc gtc cat gac ctc atc tcc agg gac tat agc 625 Leu Val Ala Phe Arg Ile Val His Asp Leu Ile Ser Arg Asp Tyr Ser 195 200 205 ctg gga ccc ttt gtg gag gag ttg ttt gaa gtg aca tcc tgt tat ttc 673 Leu Gly Pro Phe Val Glu Glu Leu Phe Glu Val Thr Ser Cys Tyr Phe 210 215 220 cct atc gat ttt acc cct cca cct aat gat ccc cat ggt atc cag aga 721 Pro Ile Asp Phe Thr Pro Pro Pro Asn Asp Pro His Gly Ile Gln Arg 225 230 235 gaa gac ctc atc ctg agt ctt cgc gct gtg ctg gct tct aca cca cga 769 Glu Asp Leu Ile Leu Ser Leu Arg Ala Val Leu Ala Ser Thr Pro Arg 240 245 250 ttt gct gag ttt ctg ctg ccc ctg ttg att gag aaa gtg gat tct gag 817 Phe Ala Glu Phe Leu Leu Pro Leu Leu Ile Glu Lys Val Asp Ser Glu 255 260 265 270 gtt ctg agt gcc aag ttg gat tct cta cag act ctg aat gct tgc tgt 865 Val Leu Ser Ala Lys Leu Asp Ser Leu Gln Thr Leu Asn Ala Cys Cys 275 280 285 gct gtg tat gga cag aag gaa ctg aag gac ttc ctc ccc agc ctt tgg 913 Ala Val Tyr Gly Gln Lys Glu Leu Lys Asp Phe Leu Pro Ser Leu Trp 290 295 300 gct tct atc cgc aga gag gtg ttc cag acg gca agt gag cgg gtg gag 961 Ala Ser Ile Arg Arg Glu Val Phe Gln Thr Ala Ser Glu Arg Val Glu 305 310 315 gca gag ggc ctg gcg gcc ctc cac tcc ctg act gcg tgt ttg tct cgc 1009 Ala Glu Gly Leu Ala Ala Leu His Ser Leu Thr Ala Cys Leu Ser Arg 320 325 330 tct gtg ctg agg gct gat gct gag gac ctc ctt gac tcc ttc ctt agc 1057 Ser Val Leu Arg Ala Asp Ala Glu Asp Leu Leu Asp Ser Phe Leu Ser 335 340 345 350 aac att cta cag gac tgc agg cac cac ctg tgt gaa ccg gac atg aaa 1105 Asn Ile Leu Gln Asp Cys Arg His His Leu Cys Glu Pro Asp Met Lys 355 360 365 ctg gtg tgg cct agt gca agc tgt tgc agg cag ctg cag gtg cat ctg 1153 Leu Val Trp Pro Ser Ala Ser Cys Cys Arg Gln Leu Gln Val His Leu 370 375 380 ccc ggg cct gtg act ctg tca cca gca atg tac tgc ctt tac tgc tgg 1201 Pro Gly Pro Val Thr Leu Ser Pro Ala Met Tyr Cys Leu Tyr Cys Trp 385 390 395 aac agt tcc aca agc aca gtc aga gca gcc agc ggc ggg aca atc ctt 1249 Asn Ser Ser Thr Ser Thr Val Arg Ala Ala Ser Gly Gly Thr Ile Leu 400 405 410 gaa atg ctc ctg ggt ttc ttg aag ctg cag cag aaa tgg agc tat gaa 1297 Glu Met Leu Leu Gly Phe Leu Lys Leu Gln Gln Lys Trp Ser Tyr Glu 415 420 425 430 gac aaa gat caa agg cct ctg aat ggc ttc aag gac cag ctg tgc tca 1345 Asp Lys Asp Gln Arg Pro Leu Asn Gly Phe Lys Asp Gln Leu Cys Ser 435 440 445 ctg gta ttc atg gct cta aca gac ccc agc acc cag ctt cag ctt gtt 1393 Leu Val Phe Met Ala Leu Thr Asp Pro Ser Thr Gln Leu Gln Leu Val 450 455 460 ggc atc cgt aca ctg aca gtc ttg ggt gcc cag cca gat ctc cta tct 1441 Gly Ile Arg Thr Leu Thr Val Leu Gly Ala Gln Pro Asp Leu Leu Ser 465 470 475 tat gag gac ttg gag ctg gca gtg ggt cac ctg tac aga ctg agc ttc 1489 Tyr Glu Asp Leu Glu Leu Ala Val Gly His Leu Tyr Arg Leu Ser Phe 480 485 490 ctg aag gag gat tcc cag agt tgc agg gtg gca gca ctg gaa gca tca 1537 Leu Lys Glu Asp Ser Gln Ser Cys Arg Val Ala Ala Leu Glu Ala Ser 495 500 505 510 gga acc ctg gct gct ctc tac cct gtg gcc ttc agc agc cac ctc gta 1585 Gly Thr Leu Ala Ala Leu Tyr Pro Val Ala Phe Ser Ser His Leu Val 515 520 525 ccc aag ctc gct gag gag ctg cgt gta ggg gag tca aat ttg act aac 1633 Pro Lys Leu Ala Glu Glu Leu Arg Val Gly Glu Ser Asn Leu Thr Asn 530 535 540 gga gat gag ccc acc caa tgc tcc cgg cat ctg tgc tgt ctg caa gcc 1681 Gly Asp Glu Pro Thr Gln Cys Ser Arg His Leu Cys Cys Leu Gln Ala 545 550 555 ttg tca gct gta tca aca cat ccc agc atc gtc aag gag aca ctg cct 1729 Leu Ser Ala Val Ser Thr His Pro Ser Ile Val Lys Glu Thr Leu Pro 560 565 570 ctg ctg ctg cag cat ctc tgg caa gtg aac aga ggg aat atg gtt gca 1777 Leu Leu Leu Gln His Leu Trp Gln Val Asn Arg Gly Asn Met Val Ala 575 580 585 590 caa tcc agt gac gtt att gct gtc tgt cag agc ctc aga cag atg gca 1825 Gln Ser Ser Asp Val Ile Ala Val Cys Gln Ser Leu Arg Gln Met Ala 595 600 605 gaa aaa tgt cag cag gac cct gag agt tgc tgg tat ttc cac cag aca 1873 Glu Lys Cys Gln Gln Asp Pro Glu Ser Cys Trp Tyr Phe His Gln Thr 610 615 620 gct ata cct tgc ctg ctt gcc ttg gct gtg cag gcc tct atg cca gag 1921 Ala Ile Pro Cys Leu Leu Ala Leu Ala Val Gln Ala Ser Met Pro Glu 625 630 635 aag gag ccc tca gtt ctg aga aaa gta cta ttg gag gat gag gtg ttg 1969 Lys Glu Pro Ser Val Leu Arg Lys Val Leu Leu Glu Asp Glu Val Leu 640 645 650 gct gcc atg gtg tct gtc att ggc act gct aca acc cac ctg agc cct 2017 Ala Ala Met Val Ser Val Ile Gly Thr Ala Thr Thr His Leu Ser Pro 655 660 665 670 gag tta gct gcc cag agt gtg aca cac att gtg ccc ctc ttc ttg gat 2065 Glu Leu Ala Ala Gln Ser Val Thr His Ile Val Pro Leu Phe Leu Asp 675 680 685 ggc aac gtg tcc ttt ctg cct gaa aac agc ttc ccg agc aga ttc cag 2113 Gly Asn Val Ser Phe Leu Pro Glu Asn Ser Phe Pro Ser Arg Phe Gln 690 695 700 cca ttc cag gat ggc tcc tca ggg cag agg cgg ctg att gca ctg ctt 2161 Pro Phe Gln Asp Gly Ser Ser Gly Gln Arg Arg Leu Ile Ala Leu Leu 705 710 715 atg gcc ttt gtc tgc tcc ctg cct cga aat ggc agc agc tgg atg aat 2209 Met Ala Phe Val Cys Ser Leu Pro Arg Asn Gly Ser Ser Trp Met Asn 720 725 730 tcc tac agc tagctgtgga caaagtggag gctggcctgg actctgggcc 2258 Ser Tyr Ser 735 ctgtcgtagt caggccttca ctcttcttct ctgggtaaca aaggccctag tgctcagata 2318 ccatcctctc agctcctgcc ttacagcccg gctcatgggc ctcctgagtg acccagaatt 2378 aggtccagca gcagctgatg gcttctctct gctcatgtct gactgcactg atgtgctgac 2438 tcgtgctggc catgccgaag tgcggatcat gttccgccag cggttcttca cagataatgt 2498 gcctgctttg gtccaagact tccatgctgc tccccaagat gtgaagccaa actacttgaa 2558 aggtctttct catgtactta acaggctgcc caagcctgta ctcttgccag agctgcccac 2618 gcttctttcc ttgctgctgg aggccctgtc ctgccctgac tgtgtggtgc agctctccac 2678 cctcagctgc cttcagcctc ttctactgga agcaccccaa gtcatgagtc ttcacgtgga 2738 caccctcgtc accaagtttc tgaacctcag ctctagccct tccatggctg tccggatcgc 2798 cgcactgcag tgcatgcatg ctctcactcg cctgcccacc cctgtgctgc tgccgtacaa 2858 accacaggtg attcgggcct tagccaaacc cctggatgac aagaagagac tggtgcgcaa 2918 ggaagcagtg tcagccagag gggagtggtt tctgttgggg agccctggca gctgagccct 2978 cagtcctggc ctagactgtt ctgacaatct aacctgggat tactaactgt tgagccatct 3038 tccccaaagc agggaaacca ctggtctctg actgcctttc ccacagacac agcacaaatg 3098 ctaggcctct gttgcatggc tgtacaaaga acataagagt ccatatttct agtggatttg 3158 taaaataagt gtgtgtgaga cacttgcgtt tgaagaaaga tctagggtcc tgggtctctt 3218 gcatttatat gtcagaaaag gggcgatatg ctgctgaggg gtgagtgcat atgagtgtgg 3278 ccctgaggac cagggctggc agatgttgtc tacctgctga g 3319 4 737 PRT Homo sapiens 4 Met Ala Ala Ala Ala Ala Val Glu Ala Ala Ala Pro Met Gly Ala Leu 1 5 10 15 Trp Gly Leu Val His Asp Phe Val Val Gly Gln Gln Glu Gly Pro Ala 20 25 30 Asp Gln Val Ala Ala Asp Val Lys Ser Gly Asn Tyr Thr Val Leu Gln 35 40 45 Val Val Glu Ala Leu Gly Ser Ser Leu Glu Asn Pro Glu Pro Arg Thr 50 55 60 Arg Ala Arg Gly Ile Gln Leu Leu Ser Gln Val Leu Leu His Cys His 65 70 75 80 Thr Leu Leu Leu Glu Lys Glu Val Val His Leu Ile Leu Phe Tyr Glu 85 90 95 Asn Arg Leu Lys Asp His His Leu Val Ile Pro Ser Val Leu Gln Gly 100 105 110 Leu Lys Ala Leu Ser Leu Cys Val Ala Leu Pro Pro Gly Leu Ala Val 115 120 125 Ser Val Leu Lys Ala Ile Phe Gln Glu Val His Val Gln Ser Leu Pro 130 135 140 Gln Val Asp Arg His Thr Val Tyr Asn Ile Ile Thr Asn Phe Met Arg 145 150 155 160 Thr Arg Glu Glu Glu Leu Lys Ser Leu Gly Ala Asp Phe Thr Phe Gly 165 170 175 Phe Ile Gln Val Met Asp Gly Glu Lys Asp Pro Arg Asn Leu Leu Val 180 185 190 Ala Phe Arg Ile Val His Asp Leu Ile Ser Arg Asp Tyr Ser Leu Gly 195 200 205 Pro Phe Val Glu Glu Leu Phe Glu Val Thr Ser Cys Tyr Phe Pro Ile 210 215 220 Asp Phe Thr Pro Pro Pro Asn Asp Pro His Gly Ile Gln Arg Glu Asp 225 230 235 240 Leu Ile Leu Ser Leu Arg Ala Val Leu Ala Ser Thr Pro Arg Phe Ala 245 250 255 Glu Phe Leu Leu Pro Leu Leu Ile Glu Lys Val Asp Ser Glu Val Leu 260 265 270 Ser Ala Lys Leu Asp Ser Leu Gln Thr Leu Asn Ala Cys Cys Ala Val 275 280 285 Tyr Gly Gln Lys Glu Leu Lys Asp Phe Leu Pro Ser Leu Trp Ala Ser 290 295 300 Ile Arg Arg Glu Val Phe Gln Thr Ala Ser Glu Arg Val Glu Ala Glu 305 310 315 320 Gly Leu Ala Ala Leu His Ser Leu Thr Ala Cys Leu Ser Arg Ser Val 325 330 335 Leu Arg Ala Asp Ala Glu Asp Leu Leu Asp Ser Phe Leu Ser Asn Ile 340 345 350 Leu Gln Asp Cys Arg His His Leu Cys Glu Pro Asp Met Lys Leu Val 355 360 365 Trp Pro Ser Ala Ser Cys Cys Arg Gln Leu Gln Val His Leu Pro Gly 370 375 380 Pro Val Thr Leu Ser Pro Ala Met Tyr Cys Leu Tyr Cys Trp Asn Ser 385 390 395 400 Ser Thr Ser Thr Val Arg Ala Ala Ser Gly Gly Thr Ile Leu Glu Met 405 410 415 Leu Leu Gly Phe Leu Lys Leu Gln Gln Lys Trp Ser Tyr Glu Asp Lys 420 425 430 Asp Gln Arg Pro Leu Asn Gly Phe Lys Asp Gln Leu Cys Ser Leu Val 435 440 445 Phe Met Ala Leu Thr Asp Pro Ser Thr Gln Leu Gln Leu Val Gly Ile 450 455 460 Arg Thr Leu Thr Val Leu Gly Ala Gln Pro Asp Leu Leu Ser Tyr Glu 465 470 475 480 Asp Leu Glu Leu Ala Val Gly His Leu Tyr Arg Leu Ser Phe Leu Lys 485 490 495 Glu Asp Ser Gln Ser Cys Arg Val Ala Ala Leu Glu Ala Ser Gly Thr 500 505 510 Leu Ala Ala Leu Tyr Pro Val Ala Phe Ser Ser His Leu Val Pro Lys 515 520 525 Leu Ala Glu Glu Leu Arg Val Gly Glu Ser Asn Leu Thr Asn Gly Asp 530 535 540 Glu Pro Thr Gln Cys Ser Arg His Leu Cys Cys Leu Gln Ala Leu Ser 545 550 555 560 Ala Val Ser Thr His Pro Ser Ile Val Lys Glu Thr Leu Pro Leu Leu 565 570 575 Leu Gln His Leu Trp Gln Val Asn Arg Gly Asn Met Val Ala Gln Ser 580 585 590 Ser Asp Val Ile Ala Val Cys Gln Ser Leu Arg Gln Met Ala Glu Lys 595 600 605 Cys Gln Gln Asp Pro Glu Ser Cys Trp Tyr Phe His Gln Thr Ala Ile 610 615 620 Pro Cys Leu Leu Ala Leu Ala Val Gln Ala Ser Met Pro Glu Lys Glu 625 630 635 640 Pro Ser Val Leu Arg Lys Val Leu Leu Glu Asp Glu Val Leu Ala Ala 645 650 655 Met Val Ser Val Ile Gly Thr Ala Thr Thr His Leu Ser Pro Glu Leu 660 665 670 Ala Ala Gln Ser Val Thr His Ile Val Pro Leu Phe Leu Asp Gly Asn 675 680 685 Val Ser Phe Leu Pro Glu Asn Ser Phe Pro Ser Arg Phe Gln Pro Phe 690 695 700 Gln Asp Gly Ser Ser Gly Gln Arg Arg Leu Ile Ala Leu Leu Met Ala 705 710 715 720 Phe Val Cys Ser Leu Pro Arg Asn Gly Ser Ser Trp Met Asn Ser Tyr 725 730 735 Ser 5 3058 DNA Homo sapiens CDS (130)..(2919) 5 gccccacagt gagaggaagg aaggcaacag tcgccagcag ccgatgtgaa gaccggactc 60 cgtgcgcccc tcgccgcctc tgcctggcca catcgatgtt gtgtccgccg cctgctcgcc 120 cggatcacg atg aag ccc cca agg cct gtc cgt acc tgc agc aaa gtt ctc 171 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu 1 5 10 ygtc ctg ctt tca ctg ctg gcc atc cac cag act act act gcc gaa aag 219 Val Leu Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys 15 20 25 30 aat ggc atc gac atc tac agc ctc acc gtg gac tcc agg gtc tca tcc 267 Asn Gly Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser 35 40 45 cga ttt gcc cac acg gtc gtc acc agc cga gtg gtc aat agg gcc aat 315 Arg Phe Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn 50 55 60 act gtg cag gag gcc acc ttc cag atg gag ctg ccc aag aaa gcc ttc 363 Thr Val Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe 65 70 75 atc acc aac ttc tcc atg atc atc gat ggc atg acc tac cca ggg atc 411 Ile Thr Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile 80 85 90 atc aag gag aag gct gaa gcc cag gca cag tac agc gca gca gtg gcc 459 Ile Lys Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala 95 100 105 110 aag gga aag agc gct ggc ctc gtc aag gcc acc ggg aga aac atg gag 507 Lys Gly Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu 115 120 125 cag ttc cag gtg tcg gtc agt gtg gct ccc aat gcc aag atc acc ttt 555 Gln Phe Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe 130 135 140 gag ctg gtc tat gag gag ctg ctc aag cgg cgt ttg ggg gtg tac gag 603 Glu Leu Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu 145 150 155 ctg ctg ctg aaa gtg cgg ccc cag cag ctg gtc aag cac ctg cag atg 651 Leu Leu Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met 160 165 170 gac att cac atc ttc gag ccc cag ggc atc agc ttt ctg gag aca gag 699 Asp Ile His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu 175 180 185 190 agc acc ttc atg acc aac cag ctg gta gac gcc ctc acc acc tgg cag 747 Ser Thr Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln 195 200 205 aat aag acc aag gct cac atc cgg ttc aag cca aca ctt tcc cag cag 795 Asn Lys Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln 210 215 220 caa aag tcc cca gag cag caa gaa aca gtc ctg gac ggc aac ctc att 843 Gln Lys Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile 225 230 235 atc cgc tat gat gtg gac cgg gcc atc tcc ggg ggc tcc att cag atc 891 Ile Arg Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile 240 245 250 gag aac ggc tac ttt gta cac tac ttt gcc ccc gag ggc cta acc aca 939 Glu Asn Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr 255 260 265 270 atg ccc aag aat gtg gtc ttt gtc att gac aag agc ggc tcc atg agt 987 Met Pro Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser 275 280 285 ggc agg aaa atc cag cag acc cgg gaa gcc cta atc aag atc ctg gat 1035 Gly Arg Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp 290 295 300 gac ctc agc ccc aga gac cag ttc aac ctc atc gtc ttc agt aca gaa 1083 Asp Leu Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu 305 310 315 gca act cag tgg agg cca tca ctg gtg cca gcc tca gcc gag aac gtg 1131 Ala Thr Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val 320 325 330 aac aag gcc agg agc ttt gct gcg ggc atc cag gcc ctg gga ggg acc 1179 Asn Lys Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr 335 340 345 350 aac atc aat gat gca atg ctg atg gct gtg cag ttg ctg gac agc agc 1227 Asn Ile Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser 355 360 365 aac cag gag gag cgg ctg ccc gaa ggg agt gtc tca ctc atc atc ctg 1275 Asn Gln Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu 370 375 380 ctc acc gat ggc gac ccc act gtg ggg gag act aac ccc agg agc atc 1323 Leu Thr Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile 385 390 395 cag aat aac gtg cgg gaa gct gta agt ggc cgg tac agc ctc ttc tgc 1371 Gln Asn Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys 400 405 410 ctg ggc ttc ggt ttc gac gtc agc tat gcc ttc ctg gag aag ctg gca 1419 Leu Gly Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala 415 420 425 430 ctg gac aat ggc ggc ctg gcc cgg cgc atc cat gag gac tca gac tct 1467 Leu Asp Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser 435 440 445 gcc ctg cag ctc cag gac ttc tac cag gaa gtg gcc aac cca ctg ctg 1515 Ala Leu Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu 450 455 460 aca gca gtg acc ttc gag tac cca agc aat gcc gtg gag gag gtc act 1563 Thr Ala Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr 465 470 475 cag aac aac ttc cgg ctc ctc ttc aag ggc tca gag atg gtg gtg gct 1611 Gln Asn Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala 480 485 490 ggg aag ctc cag gac cgg ggg cct gat gtg ctc aca gcc aca gtc agt 1659 Gly Lys Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser 495 500 505 510 ggg aag ctg cct aca cag aac atc act ttc caa acg gag tcc agt gtg 1707 Gly Lys Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val 515 520 525 gca gag cag gag gcg gag ttc cag agc ccc aag tat atc ttc cac aac 1755 Ala Glu Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn 530 535 540 ttc atg gag agg ctc tgg gca tac ctg act atc cag cag ctg ctg gag 1803 Phe Met Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu 545 550 555 caa act gtc tcc gca tcc gat gct gat cag cag gcc ctc cgg aac caa 1851 Gln Thr Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln 560 565 570 gcg ctg aat tta tca ctt gcc tac agc ttt gtc acg cct ctc aca tct 1899 Ala Leu Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser 575 580 585 590 atg gta gtc acc aaa ccc gat gac caa gag cag tct caa gtt gct gag 1947 Met Val Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu 595 600 605 aag ccc atg gaa ggc gaa agt aga aac agg aat gtc cac tca ggt tcc 1995 Lys Pro Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Gly Ser 610 615 620 act ttc ttc aaa tat tat ctc cag gga gca aaa ata cca aaa cca gag 2043 Thr Phe Phe Lys Tyr Tyr Leu Gln Gly Ala Lys Ile Pro Lys Pro Glu 625 630 635 gct tcc ttt tct cca aga aga gga tgg aat aga caa gct gga gct gct 2091 Ala Ser Phe Ser Pro Arg Arg Gly Trp Asn Arg Gln Ala Gly Ala Ala 640 645 650 ggc tcc cgg atg aat ttc aga cct ggg gtt ctc agc tcc agg caa ctt 2139 Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu 655 660 665 670 gga ctc cca gga cct cct gat gtt cct gac cat gct gct tac cac ccc 2187 Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro 675 680 685 ttc cgc cgt ctg gcc atc ttg cct gct tca gca cca cca gcc acc tca 2235 Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser 690 695 700 aat cct gat cca gct gtg tct cgt gtc atg aat atg aaa atc gaa gaa 2283 Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile Glu Glu 705 710 715 aca acc atg aca acc caa acc cca gcc ccc ata cag gct ccc tct gcc 2331 Thr Thr Met Thr Thr Gln Thr Pro Ala Pro Ile Gln Ala Pro Ser Ala 720 725 730 atc ctg cca ctg cct ggg cag agt gtg gag cgg ctc tgt gtg gac ccc 2379 Ile Leu Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro 735 740 745 750 aga cac cgc cag ggg cca gtg aac ctg ctc tca gac cct gag caa ggg 2427 Arg His Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly 755 760 765 gtt gag gtg act ggc cag tat gag agg gag aag gct ggg ttc tca tgg 2475 Val Glu Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp 770 775 780 atc gaa gtg acc ttc aag aac ccc ctg gta tgg gtt cac gca tcc cct 2523 Ile Glu Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro 785 790 795 gaa cac gtg gtg gtg act cgg aac cga aga agc tct gcg tac aag tgg 2571 Glu His Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp 800 805 810 aag gag acg cta ttc tca gtg atg ccc ggc ctg aag atg acc atg gac 2619 Lys Glu Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp 815 820 825 830 aag acg ggt ctc ctg ctg ctc agt gac cca gac aaa gtg acc atc ggc 2667 Lys Thr Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly 835 840 845 ctg ttg ttc tgg gat ggc cgt ggg gag ggg ctc cgg ctc ctt ctg cgt 2715 Leu Leu Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg 850 855 860 gac act gac cgc ttc tcc agc cac gtt gga ggg acc ctt ggc cag ttt 2763 Asp Thr Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe 865 870 875 tac cag gag gtg ctc tgg gga tct cca gca gca tca gat gac ggc aga 2811 Tyr Gln Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg 880 885 890 cgc acg ctg agg gtt cag ggc aat gac cac tct gcc acc aga gag cgc 2859 Arg Thr Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg 895 900 905 910 agg ctg gat tac cag gag ggg ccc ccg gga gtg gag att tcc tgc tgg 2907 Arg Leu Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp 915 920 925 tct gtg gag ctg tagttctgat ggaaggagct gtgcccaccc tgtacacttg 2959 Ser Val Glu Leu 930 gcttccccct gcaactgcag ggccgcttct ggggcctgga ccaccatggg gaggaagagt 3019 cccactcatt acaaataaag aaaggtggtg tgagcctga 3058 6 930 PRT Homo sapiens 6 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Gly Ser Thr Phe 610 615 620 Phe Lys Tyr Tyr Leu Gln Gly Ala Lys Ile Pro Lys Pro Glu Ala Ser 625 630 635 640 Phe Ser Pro Arg Arg Gly Trp Asn Arg Gln Ala Gly Ala Ala Gly Ser 645 650 655 Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu Gly Leu 660 665 670 Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro Phe Arg 675 680 685 Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser Asn Pro 690 695 700 Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile Glu Glu Thr Thr 705 710 715 720 Met Thr Thr Gln Thr Pro Ala Pro Ile Gln Ala Pro Ser Ala Ile Leu 725 730 735 Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro Arg His 740 745 750 Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val Glu 755 760 765 Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp Ile Glu 770 775 780 Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro Glu His 785 790 795 800 Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp Lys Glu 805 810 815 Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp Lys Thr 820 825 830 Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly Leu Leu 835 840 845 Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg Asp Thr 850 855 860 Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln 865 870 875 880 Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg Thr 885 890 895 Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg Arg Leu 900 905 910 Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp Ser Val 915 920 925 Glu Leu 930 7 2797 DNA Homo sapiens CDS (130)..(2658) 7 gccccacagt gagaggaagg aaggcaacag tcgccagcag ccgatgtgaa gaccggactc 60 cgtgcgcccc tcgccgcctc tgcctggcca catcgatgtt gtgtccgccg cctgctcgcc 120 cggatcacg atg aag ccc cca agg cct gtc cgt acc tgc agc aaa gtt ctc 171 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu 1 5 10 gtc ctg ctt tca ctg ctg gcc atc cac cag act act act gcc gaa aag 219 Val Leu Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys 15 20 25 30 aat ggc atc gac atc tac agc ctc acc gtg gac tcc agg gtc tca tcc 267 Asn Gly Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser 35 40 45 cga ttt gcc cac acg gtc gtc acc agc cga gtg gtc aat agg gcc aat 315 Arg Phe Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn 50 55 60 act gtg cag gag gcc acc ttc cag atg gag ctg ccc aag aaa gcc ttc 363 Thr Val Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe 65 70 75 atc acc aac ttc tcc atg atc atc gat ggc atg acc tac cca ggg atc 411 Ile Thr Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile 80 85 90 atc aag gag aag gct gaa gcc cag gca cag tac agc gca gca gtg gcc 459 Ile Lys Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala 95 100 105 110 aag gga aag agc gct ggc ctc gtc aag gcc acc ggg aga aac atg gag 507 Lys Gly Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu 115 120 125 cag ttc cag gtg tcg gtc agt gtg gct ccc aat gcc aag atc acc ttt 555 Gln Phe Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe 130 135 140 gag ctg gtc tat gag gag ctg ctc aag cgg cgt ttg ggg gtg tac gag 603 Glu Leu Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu 145 150 155 ctg ctg ctg aaa gtg cgg ccc cag cag ctg gtc aag cac ctg cag atg 651 Leu Leu Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met 160 165 170 gac att cac atc ttc gag ccc cag ggc atc agc ttt ctg gag aca gag 699 Asp Ile His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu 175 180 185 190 agc acc ttc atg acc aac cag ctg gta gac gcc ctc acc acc tgg cag 747 Ser Thr Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln 195 200 205 aat aag acc aag gct cac atc cgg ttc aag cca aca ctt tcc cag cag 795 Asn Lys Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln 210 215 220 caa aag tcc cca gag cag caa gaa aca gtc ctg gac ggc aac ctc att 843 Gln Lys Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile 225 230 235 atc cgc tat gat gtg gac cgg gcc atc tcc ggg ggc tcc att cag atc 891 Ile Arg Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile 240 245 250 gag aac ggc tac ttt gta cac tac ttt gcc ccc gag ggc cta acc aca 939 Glu Asn Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr 255 260 265 270 atg ccc aag aat gtg gtc ttt gtc att gac aag agc ggc tcc atg agt 987 Met Pro Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser 275 280 285 ggc agg aaa atc cag cag acc cgg gaa gcc cta atc aag atc ctg gat 1035 Gly Arg Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp 290 295 300 gac ctc agc ccc aga gac cag ttc aac ctc atc gtc ttc agt aca gaa 1083 Asp Leu Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu 305 310 315 gca act cag tgg agg cca tca ctg gtg cca gcc tca gcc gag aac gtg 1131 Ala Thr Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val 320 325 330 aac aag gcc agg agc ttt gct gcg ggc atc cag gcc ctg gga ggg acc 1179 Asn Lys Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr 335 340 345 350 aac atc aat gat gca atg ctg atg gct gtg cag ttg ctg gac agc agc 1227 Asn Ile Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser 355 360 365 aac cag gag gag cgg ctg ccc gaa ggg agt gtc tca ctc atc atc ctg 1275 Asn Gln Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu 370 375 380 ctc acc gat ggc gac ccc act gtg ggg gag act aac ccc agg agc atc 1323 Leu Thr Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile 385 390 395 cag aat aac gtg cgg gaa gct gta agt ggc cgg tac agc ctc ttc tgc 1371 Gln Asn Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys 400 405 410 ctg ggc ttc ggt ttc gac gtc agc tat gcc ttc ctg gag aag ctg gca 1419 Leu Gly Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala 415 420 425 430 ctg gac aat ggc ggc ctg gcc cgg cgc atc cat gag gac tca gac tct 1467 Leu Asp Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser 435 440 445 gcc ctg cag ctc cag gac ttc tac cag gaa gtg gcc aac cca ctg ctg 1515 Ala Leu Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu 450 455 460 aca gca gtg acc ttc gag tac cca agc aat gcc gtg gag gag gtc act 1563 Thr Ala Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr 465 470 475 cag aac aac ttc cgg ctc ctc ttc aag ggc tca gag atg gtg gtg gct 1611 Gln Asn Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala 480 485 490 ggg aag ctc cag gac cgg ggg cct gat gtg ctc aca gcc aca gtc agt 1659 Gly Lys Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser 495 500 505 510 ggg aag ctg cct aca cag aac atc act ttc caa acg gag tcc agt gtg 1707 Gly Lys Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val 515 520 525 gca gag cag gag gcg gag ttc cag agc ccc aag tat atc ttc cac aac 1755 Ala Glu Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn 530 535 540 ttc atg gag agg ctc tgg gca tac ctg act atc cag cag ctg ctg gag 1803 Phe Met Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu 545 550 555 caa act gtc tcc gca tcc gat gct gat cag cag gcc ctc cgg aac caa 1851 Gln Thr Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln 560 565 570 gcg ctg aat tta tca ctt gcc tac agc ttt gtc acg cct ctc aca tct 1899 Ala Leu Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser 575 580 585 590 atg gta gtc acc aaa ccc gat gac caa gag cag tct caa gtt gct gag 1947 Met Val Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu 595 600 605 aag ccc atg gaa ggc gaa agt aga aac agg aat gtc cac tca gct gga 1995 Lys Pro Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly 610 615 620 gct gct ggc tcc cgg atg aat ttc aga cct ggg gtt ctc agc tcc agg 2043 Ala Ala Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg 625 630 635 caa ctt gga ctc cca gga cct cct gat gtt cct gac cat gct gct tac 2091 Gln Leu Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr 640 645 650 cac ccc ttc cgc cgt ctg gcc atc ttg cct gct tca gca cca cca gcc 2139 His Pro Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala 655 660 665 670 acc tca aat cct gat cca gct gtg tct cgt gtc atg aat atg cag tat 2187 Thr Ser Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Gln Tyr 675 680 685 gag agg gag aag gct ggg ttc tca tgg atc gaa gtg acc ttc aag aac 2235 Glu Arg Glu Lys Ala Gly Phe Ser Trp Ile Glu Val Thr Phe Lys Asn 690 695 700 ccc ctg gta tgg gtt cac gca tcc cct gaa cac gtg gtg gtg act cgg 2283 Pro Leu Val Trp Val His Ala Ser Pro Glu His Val Val Val Thr Arg 705 710 715 aac cga aga agc tct gcg tac aag tgg aag gag acg cta ttc tca gtg 2331 Asn Arg Arg Ser Ser Ala Tyr Lys Trp Lys Glu Thr Leu Phe Ser Val 720 725 730 atg ccc ggc ctg aag atg acc atg gac aag acg ggt ctc ctg ctg ctc 2379 Met Pro Gly Leu Lys Met Thr Met Asp Lys Thr Gly Leu Leu Leu Leu 735 740 745 750 agt gac cca gac aaa gtg acc atc ggc ctg ttg ttc tgg gat ggc cgt 2427 Ser Asp Pro Asp Lys Val Thr Ile Gly Leu Leu Phe Trp Asp Gly Arg 755 760 765 ggg gag ggg ctc cgg ctc ctt ctg cgt gac act gac cgc ttc tcc agc 2475 Gly Glu Gly Leu Arg Leu Leu Leu Arg Asp Thr Asp Arg Phe Ser Ser 770 775 780 cac gtt gga ggg acc ctt ggc cag ttt tac cag gag gtg ctc tgg gga 2523 His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln Glu Val Leu Trp Gly 785 790 795 tct cca gca gca tca gat gac ggc aga cgc acg ctg agg gtt cag ggc 2571 Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg Thr Leu Arg Val Gln Gly 800 805 810 aat gac cac tct gcc acc aga gag cgc agg ctg gat tac cag gag ggg 2619 Asn Asp His Ser Ala Thr Arg Glu Arg Arg Leu Asp Tyr Gln Glu Gly 815 820 825 830 ccc ccg gga gtg gag att tcc tgc tgg tct gtg gag ctg tagttctgat 2668 Pro Pro Gly Val Glu Ile Ser Cys Trp Ser Val Glu Leu 835 840 ggaaggagct gtgcccaccc tgtacacttg gcttccccct gcaactgcag ggccgcttct 2728 ggggcctgga ccaccatggg gaggaagagt cccactcatt acaaataaag aaaggtggtg 2788 tgagcctga 2797 8 843 PRT Homo sapiens 8 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly Ala Ala 610 615 620 Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu 625 630 635 640 Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro 645 650 655 Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser 660 665 670 Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Gln Tyr Glu Arg 675 680 685 Glu Lys Ala Gly Phe Ser Trp Ile Glu Val Thr Phe Lys Asn Pro Leu 690 695 700 Val Trp Val His Ala Ser Pro Glu His Val Val Val Thr Arg Asn Arg 705 710 715 720 Arg Ser Ser Ala Tyr Lys Trp Lys Glu Thr Leu Phe Ser Val Met Pro 725 730 735 Gly Leu Lys Met Thr Met Asp Lys Thr Gly Leu Leu Leu Leu Ser Asp 740 745 750 Pro Asp Lys Val Thr Ile Gly Leu Leu Phe Trp Asp Gly Arg Gly Glu 755 760 765 Gly Leu Arg Leu Leu Leu Arg Asp Thr Asp Arg Phe Ser Ser His Val 770 775 780 Gly Gly Thr Leu Gly Gln Phe Tyr Gln Glu Val Leu Trp Gly Ser Pro 785 790 795 800 Ala Ala Ser Asp Asp Gly Arg Arg Thr Leu Arg Val Gln Gly Asn Asp 805 810 815 His Ser Ala Thr Arg Glu Arg Arg Leu Asp Tyr Gln Glu Gly Pro Pro 820 825 830 Gly Val Glu Ile Ser Cys Trp Ser Val Glu Leu 835 840 9 2914 DNA Homo sapiens CDS (130)..(2775) 9 gccccacagt gagaggaagg aaggcaacag tcgccagcag ccgatgtgaa gaccggactc 60 cgtgcgcccc tcgccgcctc tgcctggcca catcgatgtt gtgtccgccg cctgctcgcc 120 cggatcacg atg aag ccc cca agg cct gtc cgt acc tgc agc aaa gtt ctc 171 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu 1 5 10 gtc ctg ctt tca ctg ctg gcc atc cac cag act act act gcc gaa aag 219 Val Leu Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys 15 20 25 30 aat ggc atc gac atc tac agc ctc acc gtg gac tcc agg gtc tca tcc 267 Asn Gly Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser 35 40 45 cga ttt gcc cac acg gtc gtc acc agc cga gtg gtc aat agg gcc aat 315 Arg Phe Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn 50 55 60 act gtg cag gag gcc acc ttc cag atg gag ctg ccc aag aaa gcc ttc 363 Thr Val Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe 65 70 75 atc acc aac ttc tcc atg atc atc gat ggc atg acc tac cca ggg atc 411 Ile Thr Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile 80 85 90 atc aag gag aag gct gaa gcc cag gca cag tac agc gca gca gtg gcc 459 Ile Lys Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala 95 100 105 110 aag gga aag agc gct ggc ctc gtc aag gcc acc ggg aga aac atg gag 507 Lys Gly Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu 115 120 125 cag ttc cag gtg tcg gtc agt gtg gct ccc aat gcc aag atc acc ttt 555 Gln Phe Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe 130 135 140 gag ctg gtc tat gag gag ctg ctc aag cgg cgt ttg ggg gtg tac gag 603 Glu Leu Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu 145 150 155 ctg ctg ctg aaa gtg cgg ccc cag cag ctg gtc aag cac ctg cag atg 651 Leu Leu Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met 160 165 170 gac att cac atc ttc gag ccc cag ggc atc agc ttt ctg gag aca gag 699 Asp Ile His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu 175 180 185 190 agc acc ttc atg acc aac cag ctg gta gac gcc ctc acc acc tgg cag 747 Ser Thr Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln 195 200 205 aat aag acc aag gct cac atc cgg ttc aag cca aca ctt tcc cag cag 795 Asn Lys Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln 210 215 220 caa aag tcc cca gag cag caa gaa aca gtc ctg gac ggc aac ctc att 843 Gln Lys Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile 225 230 235 atc cgc tat gat gtg gac cgg gcc atc tcc ggg ggc tcc att cag atc 891 Ile Arg Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile 240 245 250 gag aac ggc tac ttt gta cac tac ttt gcc ccc gag ggc cta acc aca 939 Glu Asn Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr 255 260 265 270 atg ccc aag aat gtg gtc ttt gtc att gac aag agc ggc tcc atg agt 987 Met Pro Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser 275 280 285 ggc agg aaa atc cag cag acc cgg gaa gcc cta atc aag atc ctg gat 1035 Gly Arg Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp 290 295 300 gac ctc agc ccc aga gac cag ttc aac ctc atc gtc ttc agt aca gaa 1083 Asp Leu Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu 305 310 315 gca act cag tgg agg cca tca ctg gtg cca gcc tca gcc gag aac gtg 1131 Ala Thr Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val 320 325 330 aac aag gcc agg agc ttt gct gcg ggc atc cag gcc ctg gga ggg acc 1179 Asn Lys Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr 335 340 345 350 aac atc aat gat gca atg ctg atg gct gtg cag ttg ctg gac agc agc 1227 Asn Ile Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser 355 360 365 aac cag gag gag cgg ctg ccc gaa ggg agt gtc tca ctc atc atc ctg 1275 Asn Gln Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu 370 375 380 ctc acc gat ggc gac ccc act gtg ggg gag act aac ccc agg agc atc 1323 Leu Thr Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile 385 390 395 cag aat aac gtg cgg gaa gct gta agt ggc cgg tac agc ctc ttc tgc 1371 Gln Asn Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys 400 405 410 ctg ggc ttc ggt ttc gac gtc agc tat gcc ttc ctg gag aag ctg gca 1419 Leu Gly Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala 415 420 425 430 ctg gac aat ggc ggc ctg gcc cgg cgc atc cat gag gac tca gac tct 1467 Leu Asp Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser 435 440 445 gcc ctg cag ctc cag gac ttc tac cag gaa gtg gcc aac cca ctg ctg 1515 Ala Leu Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu 450 455 460 aca gca gtg acc ttc gag tac cca agc aat gcc gtg gag gag gtc act 1563 Thr Ala Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr 465 470 475 cag aac aac ttc cgg ctc ctc ttc aag ggc tca gag atg gtg gtg gct 1611 Gln Asn Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala 480 485 490 ggg aag ctc cag gac cgg ggg cct gat gtg ctc aca gcc aca gtc agt 1659 Gly Lys Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser 495 500 505 510 ggg aag ctg cct aca cag aac atc act ttc caa acg gag tcc agt gtg 1707 Gly Lys Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val 515 520 525 gca gag cag gag gcg gag ttc cag agc ccc aag tat atc ttc cac aac 1755 Ala Glu Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn 530 535 540 ttc atg gag agg ctc tgg gca tac ctg act atc cag cag ctg ctg gag 1803 Phe Met Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu 545 550 555 caa act gtc tcc gca tcc gat gct gat cag cag gcc ctc cgg aac caa 1851 Gln Thr Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln 560 565 570 gcg ctg aat tta tca ctt gcc tac agc ttt gtc acg cct ctc aca tct 1899 Ala Leu Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser 575 580 585 590 atg gta gtc acc aaa ccc gat gac caa gag cag tct caa gtt gct gag 1947 Met Val Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu 595 600 605 aag ccc atg gaa ggc gaa agt aga aac agg aat gtc cac tca gct gga 1995 Lys Pro Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly 610 615 620 gct gct ggc tcc cgg atg aat ttc aga cct ggg gtt ctc agc tcc agg 2043 Ala Ala Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg 625 630 635 caa ctt gga ctc cca gga cct cct gat gtt cct gac cat gct gct tac 2091 Gln Leu Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr 640 645 650 cac ccc ttc cgc cgt ctg gcc atc ttg cct gct tca gca aca cca gcc 2139 His Pro Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Thr Pro Ala 655 660 665 670 acc tca aat cct gat cca gct gtg tct cgt gtc atg aat atg tct gcc 2187 Thr Ser Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Ser Ala 675 680 685 atc ctg cca ctg cct ggg cag agt gtg gag cgg ctc tgt gtg gac ccc 2235 Ile Leu Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro 690 695 700 aga cac cgc cag ggg cca gtg aac ctg ctc tca gac cct gag caa ggg 2283 Arg His Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly 705 710 715 gtt gag gtg act ggc cag tat gag agg gag aag gct ggg ttc tca tgg 2331 Val Glu Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp 720 725 730 atc gaa gtg acc ttc aag aac ccc ctg gta tgg gtt cac gca tcc cct 2379 Ile Glu Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro 735 740 745 750 gaa cac gtg gtg gtg act cgg aac cga aga agc tct gcg tac aag tgg 2427 Glu His Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp 755 760 765 aag gag acg cta ttc tca gtg atg ccc ggc ctg aag atg acc atg gac 2475 Lys Glu Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp 770 775 780 aag acg ggt ctc ctg ctg ctc agt gac cca gac aaa gtg acc atc ggc 2523 Lys Thr Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly 785 790 795 ctg ttg ttc tgg gat ggc cgt ggg gag ggg ctc cgg ctc ctt ctg cgt 2571 Leu Leu Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg 800 805 810 gac act gac cgc ttc tcc agc cac gtt gga ggg acc ctt ggc cag ttt 2619 Asp Thr Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe 815 820 825 830 tac cag gag gtg ctc tgg gga tct cca gca gca tca gat gac ggc aga 2667 Tyr Gln Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg 835 840 845 cgc acg ctg agg gtt cag ggc aat gac cac tct gcc acc aga gag cgc 2715 Arg Thr Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg 850 855 860 agg ctg gat tac cag gag ggg ccc ccg gga gtg gag att tcc tgc tgg 2763 Arg Leu Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp 865 870 875 tct gtg gag ctg tagttctgat ggaaggagct gtgcccaccc tgtacacttg 2815 Ser Val Glu Leu 880 gcttccccct gcaactgcag ggccgcttct ggggcctgga ccaccatggg gaggaagagt 2875 cccactcatt acaaataaag aaaggtggtg tgagcctga 2914 10 882 PRT Homo sapiens 10 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly Ala Ala 610 615 620 Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu 625 630 635 640 Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro 645 650 655 Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Thr Pro Ala Thr Ser 660 665 670 Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Ser Ala Ile Leu 675 680 685 Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro Arg His 690 695 700 Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val Glu 705 710 715 720 Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp Ile Glu 725 730 735 Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro Glu His 740 745 750 Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp Lys Glu 755 760 765 Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp Lys Thr 770 775 780 Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly Leu Leu 785 790 795 800 Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg Asp Thr 805 810 815 Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln 820 825 830 Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg Thr 835 840 845 Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg Arg Leu 850 855 860 Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp Ser Val 865 870 875 880 Glu Leu 11 2968 DNA Homo sapiens CDS (130)..(2829) 11 gccccacagt gagaggaagg aaggcaacag tcgccagcag ccgatgtgaa gaccggactc 60 cgtgcgcccc tcgccgcctc tgcctggcca catcgatgtt gtgtccgccg cctgctcgcc 120 cggatcacg atg aag ccc cca agg cct gtc cgt acc tgc agc aaa gtt ctc 171 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu 1 5 10 gtc ctg ctt tca ctg ctg gcc atc cac cag act act act gcc gaa aag 219 Val Leu Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys 15 20 25 30 aat ggc atc gac atc tac agc ctc acc gtg gac tcc agg gtc tca tcc 267 Asn Gly Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser 35 40 45 cga ttt gcc cac acg gtc gtc acc agc cga gtg gtc aat agg gcc aat 315 Arg Phe Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn 50 55 60 act gtg cag gag gcc acc ttc cag atg gag ctg ccc aag aaa gcc ttc 363 Thr Val Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe 65 70 75 atc acc aac ttc tcc atg atc atc gat ggc atg acc tac cca ggg atc 411 Ile Thr Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile 80 85 90 atc aag gag aag gct gaa gcc cag gca cag tac agc gca gca gtg gcc 459 Ile Lys Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala 95 100 105 110 aag gga aag agc gct ggc ctc gtc aag gcc acc ggg aga aac atg gag 507 Lys Gly Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu 115 120 125 cag ttc cag gtg tcg gtc agt gtg gct ccc aat gcc aag atc acc ttt 555 Gln Phe Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe 130 135 140 gag ctg gtc tat gag gag ctg ctc aag cgg cgt ttg ggg gtg tac gag 603 Glu Leu Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu 145 150 155 ctg ctg ctg aaa gtg cgg ccc cag cag ctg gtc aag cac ctg cag atg 651 Leu Leu Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met 160 165 170 gac att cac atc ttc gag ccc cag ggc atc agc ttt ctg gag aca gag 699 Asp Ile His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu 175 180 185 190 agc acc ttc atg acc aac cag ctg gta gac gcc ctc acc acc tgg cag 747 Ser Thr Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln 195 200 205 aat aag acc aag gct cac atc cgg ttc aag cca aca ctt tcc cag cag 795 Asn Lys Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln 210 215 220 caa aag tcc cca gag cag caa gaa aca gtc ctg gac ggc aac ctc att 843 Gln Lys Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile 225 230 235 atc cgc tat gat gtg gac cgg gcc atc tcc ggg ggc tcc att cag atc 891 Ile Arg Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile 240 245 250 gag aac ggc tac ttt gta cac tac ttt gcc ccc gag ggc cta acc aca 939 Glu Asn Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr 255 260 265 270 atg ccc aag aat gtg gtc ttt gtc att gac aag agc ggc tcc atg agt 987 Met Pro Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser 275 280 285 ggc agg aaa atc cag cag acc cgg gaa gcc cta atc aag atc ctg gat 1035 Gly Arg Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp 290 295 300 gac ctc agc ccc aga gac cag ttc aac ctc atc gtc ttc agt aca gaa 1083 Asp Leu Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu 305 310 315 gca act cag tgg agg cca tca ctg gtg cca gcc tca gcc gag aac gtg 1131 Ala Thr Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val 320 325 330 aac aag gcc agg agc ttt gct gcg ggc atc cag gcc ctg gga ggg acc 1179 Asn Lys Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr 335 340 345 350 aac atc aat gat gca atg ctg atg gct gtg cag ttg ctg gac agc agc 1227 Asn Ile Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser 355 360 365 aac cag gag gag cgg ctg ccc gaa ggg agt gtc tca ctc atc atc ctg 1275 Asn Gln Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu 370 375 380 ctc acc gat ggc gac ccc act gtg ggg gag act aac ccc agg agc atc 1323 Leu Thr Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile 385 390 395 cag aat aac gtg cgg gaa gct gta agt ggc cgg tac agc ctc ttc tgc 1371 Gln Asn Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys 400 405 410 ctg ggc ttc ggt ttc gac gtc agc tat gcc ttc ctg gag aag ctg gca 1419 Leu Gly Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala 415 420 425 430 ctg gac aat ggc ggc ctg gcc cgg cgc atc cat gag gac tca gac tct 1467 Leu Asp Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser 435 440 445 gcc ctg cag ctc cag gac ttc tac cag gaa gtg gcc aac cca ctg ctg 1515 Ala Leu Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu 450 455 460 aca gca gtg acc ttc gag tac cca agc aat gcc gtg gag gag gtc act 1563 Thr Ala Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr 465 470 475 cag aac aac ttc cgg ctc ctc ttc aag ggc tca gag atg gtg gtg gct 1611 Gln Asn Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala 480 485 490 ggg aag ctc cag gac cgg ggg cct gat gtg ctc aca gcc aca gtc agt 1659 Gly Lys Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser 495 500 505 510 ggg aag ctg cct aca cag aac atc act ttc caa acg gag tcc agt gtg 1707 Gly Lys Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val 515 520 525 gca gag cag gag gcg gag ttc cag agc ccc aag tat atc ttc cac aac 1755 Ala Glu Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn 530 535 540 ttc atg gag agg ctc tgg gca tac ctg act atc cag cag ctg ctg gag 1803 Phe Met Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu 545 550 555 caa act gtc tcc gca tcc gat gct gat cag cag gcc ctc cgg aac caa 1851 Gln Thr Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln 560 565 570 gcg ctg aat tta tca ctt gcc tac agc ttt gtc acg cct ctc aca tct 1899 Ala Leu Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser 575 580 585 590 atg gta gtc acc aaa ccc gat gac caa gag cag tct caa gtt gct gag 1947 Met Val Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu 595 600 605 aag ccc atg gaa ggc gaa agt aga aac agg aat gtc cac tca gct gga 1995 Lys Pro Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly 610 615 620 gct gct ggc tcc cgg atg aat ttc aga cct ggg gtt ctc agc tcc agg 2043 Ala Ala Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg 625 630 635 caa ctt gga ctc cca gga cct cct gat gtt cct gac cat gct gct tac 2091 Gln Leu Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr 640 645 650 cac ccc ttc cgc cgt ctg gcc atc ttg cct gct tca gca cca cca gcc 2139 His Pro Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala 655 660 665 670 acc tca aat cct gat cca gct gtg tct cgt gtc atg aat atg aaa atc 2187 Thr Ser Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile 675 680 685 gaa gaa aca acc atg aca acc caa acc cca gcc ccc ata cag gct ccc 2235 Glu Glu Thr Thr Met Thr Thr Gln Thr Pro Ala Pro Ile Gln Ala Pro 690 695 700 tct gcc atc ctg cca ctg cct ggg cag agt gtg gag cgg ctc tgt gtg 2283 Ser Ala Ile Leu Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val 705 710 715 gac ccc aga cac cgc cag ggg cca gtg aac ctg ctc tca gac cct gag 2331 Asp Pro Arg His Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu 720 725 730 caa ggg gtt gag gtg act ggc cag tat gag agg gag aag gct ggg ttc 2379 Gln Gly Val Glu Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe 735 740 745 750 tca tgg atc gaa gtg acc ttc aag aac ccc ctg gta tgg gtt cac gca 2427 Ser Trp Ile Glu Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala 755 760 765 tcc cct gaa cac gtg gtg gtg act cgg aac cga aga agc tct gcg tac 2475 Ser Pro Glu His Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr 770 775 780 aag tgg aag gag acg cta ttc tca gtg atg ccc ggc ctg aag atg acc 2523 Lys Trp Lys Glu Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr 785 790 795 atg gac aag acg ggt ctc ctg ctg ctc agt gac cca gac aaa gtg acc 2571 Met Asp Lys Thr Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr 800 805 810 atc ggc ctg ttg ttc tgg gat ggc cgt ggg gag ggg ctc cgg ctc ctt 2619 Ile Gly Leu Leu Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu 815 820 825 830 ctg cgt gac act gac cgc ttc tcc agc cac gtt gga ggg acc ctt ggc 2667 Leu Arg Asp Thr Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly 835 840 845 cag ttt tac cag gag gtg ctc tgg gga tct cca gca gca tca gat gac 2715 Gln Phe Tyr Gln Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp 850 855 860 ggc aga cgc acg ctg agg gtt cag ggc aat gac cac tct gcc acc aga 2763 Gly Arg Arg Thr Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg 865 870 875 gag cgc agg ctg gat tac cag gag ggg ccc ccg gga gtg gag att tcc 2811 Glu Arg Arg Leu Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser 880 885 890 tgc tgg tct gtg gag ctg tagttctgat ggaaggagct gtgcccaccc 2859 Cys Trp Ser Val Glu Leu 895 900 tgtacacttg gcttccccct gcaactgcag ggccgcttct ggggcctgga ccaccatggg 2919 gaggaagagt cccactcatt acaaataaag aaaggtggtg tgagcctga 2968 12 900 PRT Homo sapiens 12 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly Ala Ala 610 615 620 Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu 625 630 635 640 Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro 645 650 655 Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser 660 665 670 Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile Glu Glu 675 680 685 Thr Thr Met Thr Thr Gln Thr Pro Ala Pro Ile Gln Ala Pro Ser Ala 690 695 700 Ile Leu Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro 705 710 715 720 Arg His Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly 725 730 735 Val Glu Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp 740 745 750 Ile Glu Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro 755 760 765 Glu His Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp 770 775 780 Lys Glu Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp 785 790 795 800 Lys Thr Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly 805 810 815 Leu Leu Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg 820 825 830 Asp Thr Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe 835 840 845 Tyr Gln Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg 850 855 860 Arg Thr Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg 865 870 875 880 Arg Leu Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp 885 890 895 Ser Val Glu Leu 900 13 1365 DNA Homo sapiens CDS (1)..(1362) 13 atg ctg cgg atc ctg tgc ctg gca ctc tgc agc ctg ctg act ggc acg 48 Met Leu Arg Ile Leu Cys Leu Ala Leu Cys Ser Leu Leu Thr Gly Thr 1 5 10 15 cga gct gac cct ggg gca ctg ctg cgg ttg ggc atg gac atc atg aac 96 Arg Ala Asp Pro Gly Ala Leu Leu Arg Leu Gly Met Asp Ile Met Asn 20 25 30 cgt gag gtc cag agc gcc atg gat gag agt cat atc ctg gag aag atg 144 Arg Glu Val Gln Ser Ala Met Asp Glu Ser His Ile Leu Glu Lys Met 35 40 45 gca gcc gag gca ggc aag aaa cag cca ggg atg aaa cct atc aag ggc 192 Ala Ala Glu Ala Gly Lys Lys Gln Pro Gly Met Lys Pro Ile Lys Gly 50 55 60 atc acc aat ttg aag gtg aag gat gtc cag ctg ccc gtc atc aca ctg 240 Ile Thr Asn Leu Lys Val Lys Asp Val Gln Leu Pro Val Ile Thr Leu 65 70 75 80 aac ttt gta cct gga gtg ggc atc ttc caa tgt gtg tcc aca ggc atg 288 Asn Phe Val Pro Gly Val Gly Ile Phe Gln Cys Val Ser Thr Gly Met 85 90 95 acc gtc act ggc aag agc ttc atg gga ggg aac atg gag atc atc gtg 336 Thr Val Thr Gly Lys Ser Phe Met Gly Gly Asn Met Glu Ile Ile Val 100 105 110 gcc ctg aac atc aca gcc acc aac cgg ctt ctg cgg gat gag gag aca 384 Ala Leu Asn Ile Thr Ala Thr Asn Arg Leu Leu Arg Asp Glu Glu Thr 115 120 125 ggc ctc ccc gtg ttc aag agt gag ggc tgt gag gtc atc ctg gtc aat 432 Gly Leu Pro Val Phe Lys Ser Glu Gly Cys Glu Val Ile Leu Val Asn 130 135 140 gtg aag act aac ctg cct agc aac atg ctc ccc aag atg gtc aac aag 480 Val Lys Thr Asn Leu Pro Ser Asn Met Leu Pro Lys Met Val Asn Lys 145 150 155 160 ttc ctg gac agc acc ctg cac aaa gtc ctc cct ggg ctg atg tgt ccc 528 Phe Leu Asp Ser Thr Leu His Lys Val Leu Pro Gly Leu Met Cys Pro 165 170 175 gcc atc gat gca gtc ctg gtg tat gtg aac agg aag tgg acc aac ctc 576 Ala Ile Asp Ala Val Leu Val Tyr Val Asn Arg Lys Trp Thr Asn Leu 180 185 190 agt gac ccc atg cct gtg ggc cag atg ggc acc gtc aaa tat gtt ctg 624 Ser Asp Pro Met Pro Val Gly Gln Met Gly Thr Val Lys Tyr Val Leu 195 200 205 atg tcc gca cca gcc acc aca gcc agc tac atc caa ctg gac ttc agt 672 Met Ser Ala Pro Ala Thr Thr Ala Ser Tyr Ile Gln Leu Asp Phe Ser 210 215 220 cct gtg gtg cag cag caa aag ggc aaa acc atc aag ctt gct gat gcc 720 Pro Val Val Gln Gln Gln Lys Gly Lys Thr Ile Lys Leu Ala Asp Ala 225 230 235 240 ggg gag gcc ctc acg ttc cct gag ggt tat gcc aaa ggc tcg tcg cag 768 Gly Glu Ala Leu Thr Phe Pro Glu Gly Tyr Ala Lys Gly Ser Ser Gln 245 250 255 ctg ctg ctc cca gcc acc ttc ctc tct gca gag ctt gcc ctt ctg cag 816 Leu Leu Leu Pro Ala Thr Phe Leu Ser Ala Glu Leu Ala Leu Leu Gln 260 265 270 aag tcc ttt cat gtg aat atc cag gat aca atg att ggt gag ctg ccc 864 Lys Ser Phe His Val Asn Ile Gln Asp Thr Met Ile Gly Glu Leu Pro 275 280 285 cca caa acc acc aag acc ctg gct cgc ttc att cct gaa gtg gct gta 912 Pro Gln Thr Thr Lys Thr Leu Ala Arg Phe Ile Pro Glu Val Ala Val 290 295 300 gct tat ccc aag tca aag ccc ttg acg acc cag atc aag ata aag aag 960 Ala Tyr Pro Lys Ser Lys Pro Leu Thr Thr Gln Ile Lys Ile Lys Lys 305 310 315 320 cct ccc aag gtc act atg aag aca ggc aag agc ctg ctg cac ctc cac 1008 Pro Pro Lys Val Thr Met Lys Thr Gly Lys Ser Leu Leu His Leu His 325 330 335 agc acc ctg gag atg ttc gca gct cgg tgg cgg agc aag gct cca atg 1056 Ser Thr Leu Glu Met Phe Ala Ala Arg Trp Arg Ser Lys Ala Pro Met 340 345 350 tcc ctc ttt ctc cta gaa gtg cac ttc aat ctg aag gtc cag tac tca 1104 Ser Leu Phe Leu Leu Glu Val His Phe Asn Leu Lys Val Gln Tyr Ser 355 360 365 gtg cat gag aac cag ctg cag atg gcc act tct ttg gac aga tta ctg 1152 Val His Glu Asn Gln Leu Gln Met Ala Thr Ser Leu Asp Arg Leu Leu 370 375 380 agc ttg tcc cgg aag tcc tca tcg att ggc aac ttc aat gag agg gaa 1200 Ser Leu Ser Arg Lys Ser Ser Ser Ile Gly Asn Phe Asn Glu Arg Glu 385 390 395 400 tta act ggc ttc atc acc agc tat ctc gaa gaa gcc tac atc cca gtt 1248 Leu Thr Gly Phe Ile Thr Ser Tyr Leu Glu Glu Ala Tyr Ile Pro Val 405 410 415 gtc aat gat gtg ctt caa gtg ggg ctc cca ctc ccg gac ttt ctg gcc 1296 Val Asn Asp Val Leu Gln Val Gly Leu Pro Leu Pro Asp Phe Leu Ala 420 425 430 atg aat tac aac ctg gct gag ctg gac ata gta gag ctt ggg ggc atc 1344 Met Asn Tyr Asn Leu Ala Glu Leu Asp Ile Val Glu Leu Gly Gly Ile 435 440 445 atg gaa cct gcc gac ata tga 1365 Met Glu Pro Ala Asp Ile 450 14 454 PRT Homo sapiens 14 Met Leu Arg Ile Leu Cys Leu Ala Leu Cys Ser Leu Leu Thr Gly Thr 1 5 10 15 Arg Ala Asp Pro Gly Ala Leu Leu Arg Leu Gly Met Asp Ile Met Asn 20 25 30 Arg Glu Val Gln Ser Ala Met Asp Glu Ser His Ile Leu Glu Lys Met 35 40 45 Ala Ala Glu Ala Gly Lys Lys Gln Pro Gly Met Lys Pro Ile Lys Gly 50 55 60 Ile Thr Asn Leu Lys Val Lys Asp Val Gln Leu Pro Val Ile Thr Leu 65 70 75 80 Asn Phe Val Pro Gly Val Gly Ile Phe Gln Cys Val Ser Thr Gly Met 85 90 95 Thr Val Thr Gly Lys Ser Phe Met Gly Gly Asn Met Glu Ile Ile Val 100 105 110 Ala Leu Asn Ile Thr Ala Thr Asn Arg Leu Leu Arg Asp Glu Glu Thr 115 120 125 Gly Leu Pro Val Phe Lys Ser Glu Gly Cys Glu Val Ile Leu Val Asn 130 135 140 Val Lys Thr Asn Leu Pro Ser Asn Met Leu Pro Lys Met Val Asn Lys 145 150 155 160 Phe Leu Asp Ser Thr Leu His Lys Val Leu Pro Gly Leu Met Cys Pro 165 170 175 Ala Ile Asp Ala Val Leu Val Tyr Val Asn Arg Lys Trp Thr Asn Leu 180 185 190 Ser Asp Pro Met Pro Val Gly Gln Met Gly Thr Val Lys Tyr Val Leu 195 200 205 Met Ser Ala Pro Ala Thr Thr Ala Ser Tyr Ile Gln Leu Asp Phe Ser 210 215 220 Pro Val Val Gln Gln Gln Lys Gly Lys Thr Ile Lys Leu Ala Asp Ala 225 230 235 240 Gly Glu Ala Leu Thr Phe Pro Glu Gly Tyr Ala Lys Gly Ser Ser Gln 245 250 255 Leu Leu Leu Pro Ala Thr Phe Leu Ser Ala Glu Leu Ala Leu Leu Gln 260 265 270 Lys Ser Phe His Val Asn Ile Gln Asp Thr Met Ile Gly Glu Leu Pro 275 280 285 Pro Gln Thr Thr Lys Thr Leu Ala Arg Phe Ile Pro Glu Val Ala Val 290 295 300 Ala Tyr Pro Lys Ser Lys Pro Leu Thr Thr Gln Ile Lys Ile Lys Lys 305 310 315 320 Pro Pro Lys Val Thr Met Lys Thr Gly Lys Ser Leu Leu His Leu His 325 330 335 Ser Thr Leu Glu Met Phe Ala Ala Arg Trp Arg Ser Lys Ala Pro Met 340 345 350 Ser Leu Phe Leu Leu Glu Val His Phe Asn Leu Lys Val Gln Tyr Ser 355 360 365 Val His Glu Asn Gln Leu Gln Met Ala Thr Ser Leu Asp Arg Leu Leu 370 375 380 Ser Leu Ser Arg Lys Ser Ser Ser Ile Gly Asn Phe Asn Glu Arg Glu 385 390 395 400 Leu Thr Gly Phe Ile Thr Ser Tyr Leu Glu Glu Ala Tyr Ile Pro Val 405 410 415 Val Asn Asp Val Leu Gln Val Gly Leu Pro Leu Pro Asp Phe Leu Ala 420 425 430 Met Asn Tyr Asn Leu Ala Glu Leu Asp Ile Val Glu Leu Gly Gly Ile 435 440 445 Met Glu Pro Ala Asp Ile 450 15 1374 DNA Homo sapiens CDS (1)..(1374) 15 aga tct atg ctg cgg atc ctg tgc ctg gca ctc tgc agc ctg ctg act 48 Arg Ser Met Leu Arg Ile Leu Cys Leu Ala Leu Cys Ser Leu Leu Thr 1 5 10 15 ggc acg cga gct gac cct ggg gca ctg ctg cgg ttg ggc atg gac atc 96 Gly Thr Arg Ala Asp Pro Gly Ala Leu Leu Arg Leu Gly Met Asp Ile 20 25 30 atg aac cgt gag gtc cag agc gcc atg gat gag agt cat atc ctg gag 144 Met Asn Arg Glu Val Gln Ser Ala Met Asp Glu Ser His Ile Leu Glu 35 40 45 aag atg gca gcc gag gca ggc aag aaa cag cca ggg atg aaa cct atc 192 Lys Met Ala Ala Glu Ala Gly Lys Lys Gln Pro Gly Met Lys Pro Ile 50 55 60 aag ggc atc acc aat ttg aag gtg aag gat gtc cag ctg ccc gtc atc 240 Lys Gly Ile Thr Asn Leu Lys Val Lys Asp Val Gln Leu Pro Val Ile 65 70 75 80 aca ctg aac ttt gta cct gga gtg ggc atc ttc caa tgt gtg tcc aca 288 Thr Leu Asn Phe Val Pro Gly Val Gly Ile Phe Gln Cys Val Ser Thr 85 90 95 ggc atg acc gtc act ggc aag agc ttc atg gga ggg aac atg gag atc 336 Gly Met Thr Val Thr Gly Lys Ser Phe Met Gly Gly Asn Met Glu Ile 100 105 110 atc gtg gcc ctg aac atc aca gcc acc aac cgg ctt ctg cgg gat gag 384 Ile Val Ala Leu Asn Ile Thr Ala Thr Asn Arg Leu Leu Arg Asp Glu 115 120 125 gag aca ggc ctc ccc gtg ttc aag agt gag ggc tgt gag gtc atc ctg 432 Glu Thr Gly Leu Pro Val Phe Lys Ser Glu Gly Cys Glu Val Ile Leu 130 135 140 gtc aat gtg aag act aac ctg cct agc aac atg ctc ccc aag atg gtc 480 Val Asn Val Lys Thr Asn Leu Pro Ser Asn Met Leu Pro Lys Met Val 145 150 155 160 aac aag ttc ctg gac agc acc ctg cac aaa gtc ctc cct ggg ctg atg 528 Asn Lys Phe Leu Asp Ser Thr Leu His Lys Val Leu Pro Gly Leu Met 165 170 175 tgt ccc gcc atc gat gca gtc ctg gtg tat gtg aac agg aag tgg acc 576 Cys Pro Ala Ile Asp Ala Val Leu Val Tyr Val Asn Arg Lys Trp Thr 180 185 190 aac ctc agt gac ccc atg cct gtg ggc cag atg ggc acc gtc aaa tat 624 Asn Leu Ser Asp Pro Met Pro Val Gly Gln Met Gly Thr Val Lys Tyr 195 200 205 gtt ctg atg tcc gca cca gcc acc aca gcc agc tac atc caa ctg gac 672 Val Leu Met Ser Ala Pro Ala Thr Thr Ala Ser Tyr Ile Gln Leu Asp 210 215 220 ttc agt cct gtg gtg cag cag caa aag ggc aaa acc atc aag ctt gct 720 Phe Ser Pro Val Val Gln Gln Gln Lys Gly Lys Thr Ile Lys Leu Ala 225 230 235 240 gat gcc ggg gag gcc ctc acg ttc cct gag ggt tat gcc aaa ggc tcg 768 Asp Ala Gly Glu Ala Leu Thr Phe Pro Glu Gly Tyr Ala Lys Gly Ser 245 250 255 tcg cag ctg ctg ctc cca gcc acc ttc ctc tct gca gag ctt gcc ctt 816 Ser Gln Leu Leu Leu Pro Ala Thr Phe Leu Ser Ala Glu Leu Ala Leu 260 265 270 ctg cag aag tcc ttt cat gtg aat atc cag gat aca atg att ggt gag 864 Leu Gln Lys Ser Phe His Val Asn Ile Gln Asp Thr Met Ile Gly Glu 275 280 285 ctg ccc cca caa acc acc aag acc ctg gct cgc ttc att cct gaa gtg 912 Leu Pro Pro Gln Thr Thr Lys Thr Leu Ala Arg Phe Ile Pro Glu Val 290 295 300 gct gta gct tat ccc aag tca aag ccc ttg acg acc cag atc aag ata 960 Ala Val Ala Tyr Pro Lys Ser Lys Pro Leu Thr Thr Gln Ile Lys Ile 305 310 315 320 aag aag cct ccc aag gtc act atg aag aca ggc aag agc ctg ctg cac 1008 Lys Lys Pro Pro Lys Val Thr Met Lys Thr Gly Lys Ser Leu Leu His 325 330 335 ctc cac agc acc ctg gag atg ttc gca gct cgg tgg cgg agc aag gct 1056 Leu His Ser Thr Leu Glu Met Phe Ala Ala Arg Trp Arg Ser Lys Ala 340 345 350 cca atg tcc ctc ttt ctc cta gaa gtg cac ttc aat ctg aag gtc cag 1104 Pro Met Ser Leu Phe Leu Leu Glu Val His Phe Asn Leu Lys Val Gln 355 360 365 tac tca gtg cat gag aac cag ctg cag atg gcc act tct ttg gac aga 1152 Tyr Ser Val His Glu Asn Gln Leu Gln Met Ala Thr Ser Leu Asp Arg 370 375 380 tta ctg agc ttg tcc cgg aag tcc tca tcg att ggc aac ttc aat gag 1200 Leu Leu Ser Leu Ser Arg Lys Ser Ser Ser Ile Gly Asn Phe Asn Glu 385 390 395 400 agg gaa tta act ggc ttc atc acc agc tat ctc gaa gaa gcc tac atc 1248 Arg Glu Leu Thr Gly Phe Ile Thr Ser Tyr Leu Glu Glu Ala Tyr Ile 405 410 415 cca gtt gtc aat gat gtg ctt caa gtg ggg ctc cca ctc ccg gac ttt 1296 Pro Val Val Asn Asp Val Leu Gln Val Gly Leu Pro Leu Pro Asp Phe 420 425 430 ctg gcc atg aat tac aac ctg gct gag ctg gac ata gta gag ctt ggg 1344 Leu Ala Met Asn Tyr Asn Leu Ala Glu Leu Asp Ile Val Glu Leu Gly 435 440 445 ggc atc atg gaa cct gcc gac ata ctc gag 1374 Gly Ile Met Glu Pro Ala Asp Ile Leu Glu 450 455 16 458 PRT Homo sapiens 16 Arg Ser Met Leu Arg Ile Leu Cys Leu Ala Leu Cys Ser Leu Leu Thr 1 5 10 15 Gly Thr Arg Ala Asp Pro Gly Ala Leu Leu Arg Leu Gly Met Asp Ile 20 25 30 Met Asn Arg Glu Val Gln Ser Ala Met Asp Glu Ser His Ile Leu Glu 35 40 45 Lys Met Ala Ala Glu Ala Gly Lys Lys Gln Pro Gly Met Lys Pro Ile 50 55 60 Lys Gly Ile Thr Asn Leu Lys Val Lys Asp Val Gln Leu Pro Val Ile 65 70 75 80 Thr Leu Asn Phe Val Pro Gly Val Gly Ile Phe Gln Cys Val Ser Thr 85 90 95 Gly Met Thr Val Thr Gly Lys Ser Phe Met Gly Gly Asn Met Glu Ile 100 105 110 Ile Val Ala Leu Asn Ile Thr Ala Thr Asn Arg Leu Leu Arg Asp Glu 115 120 125 Glu Thr Gly Leu Pro Val Phe Lys Ser Glu Gly Cys Glu Val Ile Leu 130 135 140 Val Asn Val Lys Thr Asn Leu Pro Ser Asn Met Leu Pro Lys Met Val 145 150 155 160 Asn Lys Phe Leu Asp Ser Thr Leu His Lys Val Leu Pro Gly Leu Met 165 170 175 Cys Pro Ala Ile Asp Ala Val Leu Val Tyr Val Asn Arg Lys Trp Thr 180 185 190 Asn Leu Ser Asp Pro Met Pro Val Gly Gln Met Gly Thr Val Lys Tyr 195 200 205 Val Leu Met Ser Ala Pro Ala Thr Thr Ala Ser Tyr Ile Gln Leu Asp 210 215 220 Phe Ser Pro Val Val Gln Gln Gln Lys Gly Lys Thr Ile Lys Leu Ala 225 230 235 240 Asp Ala Gly Glu Ala Leu Thr Phe Pro Glu Gly Tyr Ala Lys Gly Ser 245 250 255 Ser Gln Leu Leu Leu Pro Ala Thr Phe Leu Ser Ala Glu Leu Ala Leu 260 265 270 Leu Gln Lys Ser Phe His Val Asn Ile Gln Asp Thr Met Ile Gly Glu 275 280 285 Leu Pro Pro Gln Thr Thr Lys Thr Leu Ala Arg Phe Ile Pro Glu Val 290 295 300 Ala Val Ala Tyr Pro Lys Ser Lys Pro Leu Thr Thr Gln Ile Lys Ile 305 310 315 320 Lys Lys Pro Pro Lys Val Thr Met Lys Thr Gly Lys Ser Leu Leu His 325 330 335 Leu His Ser Thr Leu Glu Met Phe Ala Ala Arg Trp Arg Ser Lys Ala 340 345 350 Pro Met Ser Leu Phe Leu Leu Glu Val His Phe Asn Leu Lys Val Gln 355 360 365 Tyr Ser Val His Glu Asn Gln Leu Gln Met Ala Thr Ser Leu Asp Arg 370 375 380 Leu Leu Ser Leu Ser Arg Lys Ser Ser Ser Ile Gly Asn Phe Asn Glu 385 390 395 400 Arg Glu Leu Thr Gly Phe Ile Thr Ser Tyr Leu Glu Glu Ala Tyr Ile 405 410 415 Pro Val Val Asn Asp Val Leu Gln Val Gly Leu Pro Leu Pro Asp Phe 420 425 430 Leu Ala Met Asn Tyr Asn Leu Ala Glu Leu Asp Ile Val Glu Leu Gly 435 440 445 Gly Ile Met Glu Pro Ala Asp Ile Leu Glu 450 455 17 1226 DNA Homo sapiens CDS (1)..(1155) 17 atg ctg cgg atc ctg tgc ctg gca ctc tgc agc ctg ctg act ggc acg 48 Met Leu Arg Ile Leu Cys Leu Ala Leu Cys Ser Leu Leu Thr Gly Thr 1 5 10 15 cga gct gac cct ggg gca ctg ctg cgg ttg ggc atg gac atc atg aac 96 Arg Ala Asp Pro Gly Ala Leu Leu Arg Leu Gly Met Asp Ile Met Asn 20 25 30 cgt gag gtc cag agc gcc atg gat gag agt cat atc ctg gag aag atg 144 Arg Glu Val Gln Ser Ala Met Asp Glu Ser His Ile Leu Glu Lys Met 35 40 45 gca gcc gag gca ggc aag aaa cag cca ggg atg aaa cct atc aag ggc 192 Ala Ala Glu Ala Gly Lys Lys Gln Pro Gly Met Lys Pro Ile Lys Gly 50 55 60 atc acc aat ttg aag gtg aag gat gtc cag ctg ccc gtc atc aca ctg 240 Ile Thr Asn Leu Lys Val Lys Asp Val Gln Leu Pro Val Ile Thr Leu 65 70 75 80 aac ttt gta cct gga gtg ggc atc ttc caa tgt gtg tcc aca ggc atg 288 Asn Phe Val Pro Gly Val Gly Ile Phe Gln Cys Val Ser Thr Gly Met 85 90 95 acc gtc act ggc aag agc ttc atg gga ggg aac atg gag atc atc gtg 336 Thr Val Thr Gly Lys Ser Phe Met Gly Gly Asn Met Glu Ile Ile Val 100 105 110 gcc ctg aac atc aca gcc acc aac cgg ctt ctg cgg gat gag gag aca 384 Ala Leu Asn Ile Thr Ala Thr Asn Arg Leu Leu Arg Asp Glu Glu Thr 115 120 125 ggc ctc ccc gtg ttc aag agt gag ggc tgt gag gtc atc ctg gtc aat 432 Gly Leu Pro Val Phe Lys Ser Glu Gly Cys Glu Val Ile Leu Val Asn 130 135 140 gtg aag act aac ctg cct agc aac atg ctc ccc aag atg gtc aac aag 480 Val Lys Thr Asn Leu Pro Ser Asn Met Leu Pro Lys Met Val Asn Lys 145 150 155 160 ttc ctg gac agc acc ctg cac aaa gtc ctc cct ggg ctg atg tgt ccc 528 Phe Leu Asp Ser Thr Leu His Lys Val Leu Pro Gly Leu Met Cys Pro 165 170 175 gcc atc gat gca gtc ctg gtg tat gtg aac agg aag tgg acc aac ctc 576 Ala Ile Asp Ala Val Leu Val Tyr Val Asn Arg Lys Trp Thr Asn Leu 180 185 190 agt gac ccc atg cct gtg ggc cag atg ggc acc gtc aaa tat gtt ctg 624 Ser Asp Pro Met Pro Val Gly Gln Met Gly Thr Val Lys Tyr Val Leu 195 200 205 atg tcc gca cca gcc acc aca gcc agc tac atc caa ctg gac ttc agt 672 Met Ser Ala Pro Ala Thr Thr Ala Ser Tyr Ile Gln Leu Asp Phe Ser 210 215 220 cct gtg gtg cag cag caa aag ggc aaa acc atc aag ctt gct gat gcc 720 Pro Val Val Gln Gln Gln Lys Gly Lys Thr Ile Lys Leu Ala Asp Ala 225 230 235 240 ggg gag gcc ctc acg ttc cct gag ggt tat gcc aaa ggc tcg tcg cag 768 Gly Glu Ala Leu Thr Phe Pro Glu Gly Tyr Ala Lys Gly Ser Ser Gln 245 250 255 ctg ctg ctc cca gcc acc ttc ctc tct gca gag ctt gcc ctt ctg cag 816 Leu Leu Leu Pro Ala Thr Phe Leu Ser Ala Glu Leu Ala Leu Leu Gln 260 265 270 aag tcc ttt cat gtg aat atc cag gat aca atg att ggt gag ctg ccc 864 Lys Ser Phe His Val Asn Ile Gln Asp Thr Met Ile Gly Glu Leu Pro 275 280 285 cca caa acc acc aag acc ctg gct cgc ttc att cct gaa gtg gct gta 912 Pro Gln Thr Thr Lys Thr Leu Ala Arg Phe Ile Pro Glu Val Ala Val 290 295 300 gct tat ccc aag tca aag ccc ttg acg acc cag atc aag ata aag aag 960 Ala Tyr Pro Lys Ser Lys Pro Leu Thr Thr Gln Ile Lys Ile Lys Lys 305 310 315 320 cct ccc aag gtc act atg aag aca ggc aag agc ctg ctg cac ctc cac 1008 Pro Pro Lys Val Thr Met Lys Thr Gly Lys Ser Leu Leu His Leu His 325 330 335 agc acc ctg gag atg ttc gca gct cgg tgg cgg agc aag gct cca atg 1056 Ser Thr Leu Glu Met Phe Ala Ala Arg Trp Arg Ser Lys Ala Pro Met 340 345 350 tcc ctc ttt ctc cta gaa gtg cac ttc aat ctg aag gtc cag tac tca 1104 Ser Leu Phe Leu Leu Glu Val His Phe Asn Leu Lys Val Gln Tyr Ser 355 360 365 gtg cat gag aac cag ctg cag atg gcc act tct ttg gac agg aga ggg 1152 Val His Glu Asn Gln Leu Gln Met Ala Thr Ser Leu Asp Arg Arg Gly 370 375 380 aat taactggctt catcaccagc tatctcgaag agcctacatc ccagttgtca 1205 Asn 385 atgatgtgct ttcagtgggc t 1226 18 385 PRT Homo sapiens 18 Met Leu Arg Ile Leu Cys Leu Ala Leu Cys Ser Leu Leu Thr Gly Thr 1 5 10 15 Arg Ala Asp Pro Gly Ala Leu Leu Arg Leu Gly Met Asp Ile Met Asn 20 25 30 Arg Glu Val Gln Ser Ala Met Asp Glu Ser His Ile Leu Glu Lys Met 35 40 45 Ala Ala Glu Ala Gly Lys Lys Gln Pro Gly Met Lys Pro Ile Lys Gly 50 55 60 Ile Thr Asn Leu Lys Val Lys Asp Val Gln Leu Pro Val Ile Thr Leu 65 70 75 80 Asn Phe Val Pro Gly Val Gly Ile Phe Gln Cys Val Ser Thr Gly Met 85 90 95 Thr Val Thr Gly Lys Ser Phe Met Gly Gly Asn Met Glu Ile Ile Val 100 105 110 Ala Leu Asn Ile Thr Ala Thr Asn Arg Leu Leu Arg Asp Glu Glu Thr 115 120 125 Gly Leu Pro Val Phe Lys Ser Glu Gly Cys Glu Val Ile Leu Val Asn 130 135 140 Val Lys Thr Asn Leu Pro Ser Asn Met Leu Pro Lys Met Val Asn Lys 145 150 155 160 Phe Leu Asp Ser Thr Leu His Lys Val Leu Pro Gly Leu Met Cys Pro 165 170 175 Ala Ile Asp Ala Val Leu Val Tyr Val Asn Arg Lys Trp Thr Asn Leu 180 185 190 Ser Asp Pro Met Pro Val Gly Gln Met Gly Thr Val Lys Tyr Val Leu 195 200 205 Met Ser Ala Pro Ala Thr Thr Ala Ser Tyr Ile Gln Leu Asp Phe Ser 210 215 220 Pro Val Val Gln Gln Gln Lys Gly Lys Thr Ile Lys Leu Ala Asp Ala 225 230 235 240 Gly Glu Ala Leu Thr Phe Pro Glu Gly Tyr Ala Lys Gly Ser Ser Gln 245 250 255 Leu Leu Leu Pro Ala Thr Phe Leu Ser Ala Glu Leu Ala Leu Leu Gln 260 265 270 Lys Ser Phe His Val Asn Ile Gln Asp Thr Met Ile Gly Glu Leu Pro 275 280 285 Pro Gln Thr Thr Lys Thr Leu Ala Arg Phe Ile Pro Glu Val Ala Val 290 295 300 Ala Tyr Pro Lys Ser Lys Pro Leu Thr Thr Gln Ile Lys Ile Lys Lys 305 310 315 320 Pro Pro Lys Val Thr Met Lys Thr Gly Lys Ser Leu Leu His Leu His 325 330 335 Ser Thr Leu Glu Met Phe Ala Ala Arg Trp Arg Ser Lys Ala Pro Met 340 345 350 Ser Leu Phe Leu Leu Glu Val His Phe Asn Leu Lys Val Gln Tyr Ser 355 360 365 Val His Glu Asn Gln Leu Gln Met Ala Thr Ser Leu Asp Arg Arg Gly 370 375 380 Asn 385 19 765 DNA Homo sapiens CDS (10)..(756) 19 tcgcccttc atg gtg atg tcc cag gcc acc tac acg ttc ctc acg tgc ttc 51 Met Val Met Ser Gln Ala Thr Tyr Thr Phe Leu Thr Cys Phe 1 5 10 gcc ggc ttc tgg ctc atc tgg ggt ctc atc gtc ctg ctc tgc tgc ttc 99 Ala Gly Phe Trp Leu Ile Trp Gly Leu Ile Val Leu Leu Cys Cys Phe 15 20 25 30 tgc agc ttc ctg cgc cgc cgc ctc aaa cgg cgc cag gag gag cga ctg 147 Cys Ser Phe Leu Arg Arg Arg Leu Lys Arg Arg Gln Glu Glu Arg Leu 35 40 45 cgc gag cag aac ctg cgc gcc cta gag ctg gag ccc ctc gaa ctc gag 195 Arg Glu Gln Asn Leu Arg Ala Leu Glu Leu Glu Pro Leu Glu Leu Glu 50 55 60 ggc agt ctg gcc ggg agc ccc ccg ggc ctg gcg ccg ccg cag cca cca 243 Gly Ser Leu Ala Gly Ser Pro Pro Gly Leu Ala Pro Pro Gln Pro Pro 65 70 75 cca cac cgt agc cgc ctg gag gcg ccg gct cac gcg cac tcg cat ccg 291 Pro His Arg Ser Arg Leu Glu Ala Pro Ala His Ala His Ser His Pro 80 85 90 cac gtg cac gtg cac ccg ccg cct acg cac ctg tcg gtg ccg cca cgg 339 His Val His Val His Pro Pro Pro Thr His Leu Ser Val Pro Pro Arg 95 100 105 110 ccc tgg agc tac ccg cgc caa gcg gaa tcg gac atg tcc aaa cca ccg 387 Pro Trp Ser Tyr Pro Arg Gln Ala Glu Ser Asp Met Ser Lys Pro Pro 115 120 125 tgt tac gaa gag gcg gtg ctg atg gca gag ccg ccg ccg ccc tat agc 435 Cys Tyr Glu Glu Ala Val Leu Met Ala Glu Pro Pro Pro Pro Tyr Ser 130 135 140 gag gtg ctc acg gac acg cgc ggc ctc tac cgc aag atc gtc acg ccc 483 Glu Val Leu Thr Asp Thr Arg Gly Leu Tyr Arg Lys Ile Val Thr Pro 145 150 155 ttc ctg agt cgc cgc gac agc gcg gag aag cag gag cag ccg cct ccc 531 Phe Leu Ser Arg Arg Asp Ser Ala Glu Lys Gln Glu Gln Pro Pro Pro 160 165 170 agc tac aag ccg ctc ttc ctg gac cgg ggc tac acc tcg gcg ctg cac 579 Ser Tyr Lys Pro Leu Phe Leu Asp Arg Gly Tyr Thr Ser Ala Leu His 175 180 185 190 ctg ccc agc gcc cct cgg ccc gcg ccg ccc tgc cca gcc ctc tgc ctg 627 Leu Pro Ser Ala Pro Arg Pro Ala Pro Pro Cys Pro Ala Leu Cys Leu 195 200 205 cag gcc gac cgt ggc cgc cgg gtc ttc ccc agc tgg acc gac tca gag 675 Gln Ala Asp Arg Gly Arg Arg Val Phe Pro Ser Trp Thr Asp Ser Glu 210 215 220 ctc agc agc cgc gag ccc ctg gag cac gga gct tgg cgt ctg ccg gtc 723 Leu Ser Ser Arg Glu Pro Leu Glu His Gly Ala Trp Arg Leu Pro Val 225 230 235 tcc atc ccc ttg ttc ggg agg act aca gcc gta tagaggggc 765 Ser Ile Pro Leu Phe Gly Arg Thr Thr Ala Val 240 245 20 249 PRT Homo sapiens 20 Met Val Met Ser Gln Ala Thr Tyr Thr Phe Leu Thr Cys Phe Ala Gly 1 5 10 15 Phe Trp Leu Ile Trp Gly Leu Ile Val Leu Leu Cys Cys Phe Cys Ser 20 25 30 Phe Leu Arg Arg Arg Leu Lys Arg Arg Gln Glu Glu Arg Leu Arg Glu 35 40 45 Gln Asn Leu Arg Ala Leu Glu Leu Glu Pro Leu Glu Leu Glu Gly Ser 50 55 60 Leu Ala Gly Ser Pro Pro Gly Leu Ala Pro Pro Gln Pro Pro Pro His 65 70 75 80 Arg Ser Arg Leu Glu Ala Pro Ala His Ala His Ser His Pro His Val 85 90 95 His Val His Pro Pro Pro Thr His Leu Ser Val Pro Pro Arg Pro Trp 100 105 110 Ser Tyr Pro Arg Gln Ala Glu Ser Asp Met Ser Lys Pro Pro Cys Tyr 115 120 125 Glu Glu Ala Val Leu Met Ala Glu Pro Pro Pro Pro Tyr Ser Glu Val 130 135 140 Leu Thr Asp Thr Arg Gly Leu Tyr Arg Lys Ile Val Thr Pro Phe Leu 145 150 155 160 Ser Arg Arg Asp Ser Ala Glu Lys Gln Glu Gln Pro Pro Pro Ser Tyr 165 170 175 Lys Pro Leu Phe Leu Asp Arg Gly Tyr Thr Ser Ala Leu His Leu Pro 180 185 190 Ser Ala Pro Arg Pro Ala Pro Pro Cys Pro Ala Leu Cys Leu Gln Ala 195 200 205 Asp Arg Gly Arg Arg Val Phe Pro Ser Trp Thr Asp Ser Glu Leu Ser 210 215 220 Ser Arg Glu Pro Leu Glu His Gly Ala Trp Arg Leu Pro Val Ser Ile 225 230 235 240 Pro Leu Phe Gly Arg Thr Thr Ala Val 245 21 1126 DNA Homo sapiens CDS (119)..(577) 21 ggcacgaggc ccgcgcgcgg gggcgcccag gccactgggc tccgcggagc cagcgagagg 60 tctgcgcgga gtctgagcgg cgctcgtccc gtcccaaggc cgacgccagc acgccgtc 118 atg gcc ccc gca gcg gcg acg ggg ggc agc acc ctg ccc agt ggc ttc 166 Met Ala Pro Ala Ala Ala Thr Gly Gly Ser Thr Leu Pro Ser Gly Phe 1 5 10 15 tcg gtc ttc acc acc ttg ccc gac ttg ctc ttc atc ttt gag ttt atc 214 Ser Val Phe Thr Thr Leu Pro Asp Leu Leu Phe Ile Phe Glu Phe Ile 20 25 30 ttc ggg ggc ctg gtg tgg atc ctg gtg gcc tcc tcc ctg gtg ccc tgg 262 Phe Gly Gly Leu Val Trp Ile Leu Val Ala Ser Ser Leu Val Pro Trp 35 40 45 ccc ctg gtc cag ggc tgg gtg atg ttc gtg tct gtg ttc tgc ttc gtg 310 Pro Leu Val Gln Gly Trp Val Met Phe Val Ser Val Phe Cys Phe Val 50 55 60 gcc acc acc acc ttg atc atc ctg tac ata att gga gcc cac ggt gga 358 Ala Thr Thr Thr Leu Ile Ile Leu Tyr Ile Ile Gly Ala His Gly Gly 65 70 75 80 gag act tcc tgg gtc acc ttg gac gca gcc tac cac tgc acc gct gcc 406 Glu Thr Ser Trp Val Thr Leu Asp Ala Ala Tyr His Cys Thr Ala Ala 85 90 95 ctc ttt tac ctc agc gcc tca gtc ctg gag gcc ctg gcc acc atc acg 454 Leu Phe Tyr Leu Ser Ala Ser Val Leu Glu Ala Leu Ala Thr Ile Thr 100 105 110 atg caa gac ggc ttc acc tac agg cac tac cat gaa aac att gct gcc 502 Met Gln Asp Gly Phe Thr Tyr Arg His Tyr His Glu Asn Ile Ala Ala 115 120 125 gtg gtg ttc tcc tac ata gcc act ctg ctc tac gtg gtc cat gcg gtg 550 Val Val Phe Ser Tyr Ile Ala Thr Leu Leu Tyr Val Val His Ala Val 130 135 140 ttc tct tta atc aga tgg aag tct tca taaagccgca gtagaacttg 597 Phe Ser Leu Ile Arg Trp Lys Ser Ser 145 150 agctgaaaac ccagatggtg ttaactggcc gccccacttt ccggcataac tttttagaaa 657 acagaaatgc ccttgatggt ggaaaaaaga aaacaaccac ccccccactg cccaaaaaaa 717 aaagccctgc cctgttgctc gtgggtgctg tgtttactct cccgtgtgcc ttcgcgtccg 777 ggttgggagc ttgctgtgtc taacctccaa ctgctgtgct gtctgctagg gtcacctcct 837 gtttgtgaaa ggggaccttc ttgttcgggg gtgggaagtg gcgaccgtga cctgagaagg 897 aaagaaagat cctctgctga cccctggagc agctctcgag aactacctgt tggtattgtc 957 cacaagctct cccgagcgcc ccatcttgtg ccatgtttta agtcttcatg gatgttctgc 1017 atgtcatggg gactaaaact cacccaacag atctttccag aggtccatgg tggaagacga 1077 taaccctgtg aaatacttta taaaatgtct taatgttcaa aaaaaaaaa 1126 22 153 PRT Homo sapiens 22 Met Ala Pro Ala Ala Ala Thr Gly Gly Ser Thr Leu Pro Ser Gly Phe 1 5 10 15 Ser Val Phe Thr Thr Leu Pro Asp Leu Leu Phe Ile Phe Glu Phe Ile 20 25 30 Phe Gly Gly Leu Val Trp Ile Leu Val Ala Ser Ser Leu Val Pro Trp 35 40 45 Pro Leu Val Gln Gly Trp Val Met Phe Val Ser Val Phe Cys Phe Val 50 55 60 Ala Thr Thr Thr Leu Ile Ile Leu Tyr Ile Ile Gly Ala His Gly Gly 65 70 75 80 Glu Thr Ser Trp Val Thr Leu Asp Ala Ala Tyr His Cys Thr Ala Ala 85 90 95 Leu Phe Tyr Leu Ser Ala Ser Val Leu Glu Ala Leu Ala Thr Ile Thr 100 105 110 Met Gln Asp Gly Phe Thr Tyr Arg His Tyr His Glu Asn Ile Ala Ala 115 120 125 Val Val Phe Ser Tyr Ile Ala Thr Leu Leu Tyr Val Val His Ala Val 130 135 140 Phe Ser Leu Ile Arg Trp Lys Ser Ser 145 150 23 464 DNA Homo sapiens CDS (119)..(409) 23 ggcacgaggc ccgcgcgcgg gggcgcccag gccactgggc tccgcggagc cagcgagagg 60 tctgcgcgga gtctgagcgg cgctcgtccc gtcccaaggc cgacgccagc acgccgtc 118 atg gcc ccc gca gcg gcg acg ggg ggc agc acc ctg ccc agt ggc ttc 166 Met Ala Pro Ala Ala Ala Thr Gly Gly Ser Thr Leu Pro Ser Gly Phe 1 5 10 15 tcg gtc ttc acc acc ttg ccc gac ttg ctc ttc atc ttt gag ttt gac 214 Ser Val Phe Thr Thr Leu Pro Asp Leu Leu Phe Ile Phe Glu Phe Asp 20 25 30 gca acc tac cac tgc acc gct gcc ctc ttt tac ctc agc gcc tca gtc 262 Ala Thr Tyr His Cys Thr Ala Ala Leu Phe Tyr Leu Ser Ala Ser Val 35 40 45 ctg gag gcc ctg gcc acc atc acg atg caa gac ggc ttc acc tac agg 310 Leu Glu Ala Leu Ala Thr Ile Thr Met Gln Asp Gly Phe Thr Tyr Arg 50 55 60 cac tac cat gaa aac att gct gcc gtg gtg ttc tcc tac ata gcc act 358 His Tyr His Glu Asn Ile Ala Ala Val Val Phe Ser Tyr Ile Ala Thr 65 70 75 80 ctg ctc tac gtg gtc cat gcg gtg ttc tct tta atc aga tgg aag tct 406 Leu Leu Tyr Val Val His Ala Val Phe Ser Leu Ile Arg Trp Lys Ser 85 90 95 tca taaagccgca gtagaacttg agctgaaaac ccagatggtg ttaactggcc gcccc 464 Ser 24 97 PRT Homo sapiens 24 Met Ala Pro Ala Ala Ala Thr Gly Gly Ser Thr Leu Pro Ser Gly Phe 1 5 10 15 Ser Val Phe Thr Thr Leu Pro Asp Leu Leu Phe Ile Phe Glu Phe Asp 20 25 30 Ala Thr Tyr His Cys Thr Ala Ala Leu Phe Tyr Leu Ser Ala Ser Val 35 40 45 Leu Glu Ala Leu Ala Thr Ile Thr Met Gln Asp Gly Phe Thr Tyr Arg 50 55 60 His Tyr His Glu Asn Ile Ala Ala Val Val Phe Ser Tyr Ile Ala Thr 65 70 75 80 Leu Leu Tyr Val Val His Ala Val Phe Ser Leu Ile Arg Trp Lys Ser 85 90 95 Ser 25 4801 DNA Homo sapiens CDS (178)..(3639) 25 ccgctgcggg ctcgggcgcc gcagcgcgcc ggcccgagcc cctggacgag gcccacggag 60 ccgctcgccc cgacccagcc gcccgatgtc ctcaaaatgg aggcagcggg ggcggcggcg 120 tgaagaaagc ggcgctgtgg gcgcgggagt aggggcccgg gcggaggcgg tggcggg 177 atg ggg ctg ctg ctc atg atc ctg gcg tcg gcc gtg ctg ggt tcc ttc 225 Met Gly Leu Leu Leu Met Ile Leu Ala Ser Ala Val Leu Gly Ser Phe 1 5 10 15 ctc acg ctc ctc gcc cag ttc ttc ctg ctg tac cgc aga cag ccc gag 273 Leu Thr Leu Leu Ala Gln Phe Phe Leu Leu Tyr Arg Arg Gln Pro Glu 20 25 30 ccg ccg gcg gac gag gcc gcc cgc gcg ggc gag ggc ttc cgc tac atc 321 Pro Pro Ala Asp Glu Ala Ala Arg Ala Gly Glu Gly Phe Arg Tyr Ile 35 40 45 aag cca gtg ccg ggc ctg ctc cta agg gag tac ctt tat ggc ggc ggc 369 Lys Pro Val Pro Gly Leu Leu Leu Arg Glu Tyr Leu Tyr Gly Gly Gly 50 55 60 cgg gat gag gag ccc tcc gga gcg gcc cct gag ggc ggc gcg acc ccc 417 Arg Asp Glu Glu Pro Ser Gly Ala Ala Pro Glu Gly Gly Ala Thr Pro 65 70 75 80 acc gcg gcc ccc gag acc ccc gcc ccg ccg acg cgg gag act tgc tac 465 Thr Ala Ala Pro Glu Thr Pro Ala Pro Pro Thr Arg Glu Thr Cys Tyr 85 90 95 ttc ctc aac gcc acc atc cta ttc ctg ttc cgg gag ttg cgg gac acc 513 Phe Leu Asn Ala Thr Ile Leu Phe Leu Phe Arg Glu Leu Arg Asp Thr 100 105 110 gcg ctg acc cgc cgc tgg gtc acc aag aag atc aag gtg gag ttc gag 561 Ala Leu Thr Arg Arg Trp Val Thr Lys Lys Ile Lys Val Glu Phe Glu 115 120 125 gag ctg ctg cag acc aag acg gcc ggg cgc ctg ctg gag ggg ctg agc 609 Glu Leu Leu Gln Thr Lys Thr Ala Gly Arg Leu Leu Glu Gly Leu Ser 130 135 140 ctg cgg gac gtg ttc ctg ggc gag acg gtg ccc ttc atc aag acc atc 657 Leu Arg Asp Val Phe Leu Gly Glu Thr Val Pro Phe Ile Lys Thr Ile 145 150 155 160 cgg ctc gtg cgg cca gtc gtg ccc tcg gcc acc ggg gag ccc gat ggc 705 Arg Leu Val Arg Pro Val Val Pro Ser Ala Thr Gly Glu Pro Asp Gly 165 170 175 cct gaa ggg gag gcg ctg ccc gcc gcc tgc ccc gag gag ctg gcc ttc 753 Pro Glu Gly Glu Ala Leu Pro Ala Ala Cys Pro Glu Glu Leu Ala Phe 180 185 190 gag gcg gag gtg gag tac aac ggg ggc ttc cac ctg gcc atc gac gtg 801 Glu Ala Glu Val Glu Tyr Asn Gly Gly Phe His Leu Ala Ile Asp Val 195 200 205 gac ctg gtc ttc ggc aag tcc gcc tac ttg ttt gtc aag ctg tcc cgc 849 Asp Leu Val Phe Gly Lys Ser Ala Tyr Leu Phe Val Lys Leu Ser Arg 210 215 220 gtg gtg gga agg ctg cgc ttg gtc ttt acg cgc gtg ccc ttc acc cac 897 Val Val Gly Arg Leu Arg Leu Val Phe Thr Arg Val Pro Phe Thr His 225 230 235 240 tgg ttc ttc tcc ttc gtg gaa gac ccg ctg atc gac ttc gag gtg cgc 945 Trp Phe Phe Ser Phe Val Glu Asp Pro Leu Ile Asp Phe Glu Val Arg 245 250 255 tcc cag ttt gaa ggg cgg ccc atg ccc cag ctc acc tcc atc atc gtc 993 Ser Gln Phe Glu Gly Arg Pro Met Pro Gln Leu Thr Ser Ile Ile Val 260 265 270 aac cag ctc aag aag atc atc aag cgc aag cac acc cta ccg aat tac 1041 Asn Gln Leu Lys Lys Ile Ile Lys Arg Lys His Thr Leu Pro Asn Tyr 275 280 285 aag atc agg ttt aag ccg ttt ttt cca tac cag acc ttg caa gga ttt 1089 Lys Ile Arg Phe Lys Pro Phe Phe Pro Tyr Gln Thr Leu Gln Gly Phe 290 295 300 gaa gaa gat gaa gag cat atc cat ata caa caa tgg gca ctt act gaa 1137 Glu Glu Asp Glu Glu His Ile His Ile Gln Gln Trp Ala Leu Thr Glu 305 310 315 320 ggc cgt ctt aaa gtt acg ttg tta gaa tgt agc agg tta ctc att ttt 1185 Gly Arg Leu Lys Val Thr Leu Leu Glu Cys Ser Arg Leu Leu Ile Phe 325 330 335 gga tcc tat gac aga gag gca aat gtt cat tgc aca ctt gag tta agc 1233 Gly Ser Tyr Asp Arg Glu Ala Asn Val His Cys Thr Leu Glu Leu Ser 340 345 350 agt agt gtt tgg gaa gaa aaa cag agg agt tct att aag acg gtt gaa 1281 Ser Ser Val Trp Glu Glu Lys Gln Arg Ser Ser Ile Lys Thr Val Glu 355 360 365 tta ata aaa gga aat tta caa agt gtt gga ctt aca ctt cgt ctt gtc 1329 Leu Ile Lys Gly Asn Leu Gln Ser Val Gly Leu Thr Leu Arg Leu Val 370 375 380 cag tca act gat ggg tat gct ggg cac gtc atc att gaa act gtg gct 1377 Gln Ser Thr Asp Gly Tyr Ala Gly His Val Ile Ile Glu Thr Val Ala 385 390 395 400 cca aac tcg cct gct gca att gca gat ctt cag cgg gga gat cga ctt 1425 Pro Asn Ser Pro Ala Ala Ile Ala Asp Leu Gln Arg Gly Asp Arg Leu 405 410 415 atc gcc att gga ggt gtg aaa atc aca tca aca ctg caa gtg ttg aag 1473 Ile Ala Ile Gly Gly Val Lys Ile Thr Ser Thr Leu Gln Val Leu Lys 420 425 430 ctt atc aag cag gct ggt gac cga gtc ctg gtg tac tat gaa agg cct 1521 Leu Ile Lys Gln Ala Gly Asp Arg Val Leu Val Tyr Tyr Glu Arg Pro 435 440 445 gtt ggc cag agt aat caa ggt gca gtg ctg caa gat aac ttt ggc cag 1569 Val Gly Gln Ser Asn Gln Gly Ala Val Leu Gln Asp Asn Phe Gly Gln 450 455 460 ttg gaa gaa aac ttt ttg tca agc tca tgc caa tcg ggt tat gaa gag 1617 Leu Glu Glu Asn Phe Leu Ser Ser Ser Cys Gln Ser Gly Tyr Glu Glu 465 470 475 480 gaa gct gcc ggg ttg aca gta gat act gaa agt aga gag ctg gat tct 1665 Glu Ala Ala Gly Leu Thr Val Asp Thr Glu Ser Arg Glu Leu Asp Ser 485 490 495 gaa ttt gaa gac ttg gca agt gat gtc aga gca caa aat gag ttc aaa 1713 Glu Phe Glu Asp Leu Ala Ser Asp Val Arg Ala Gln Asn Glu Phe Lys 500 505 510 gat gag gca caa tca tta agt cat agt ccc aaa cgt gtt cca aca aca 1761 Asp Glu Ala Gln Ser Leu Ser His Ser Pro Lys Arg Val Pro Thr Thr 515 520 525 ctt tct att aaa ccc ctt gga gct ata tca cca gtt tta aac cgt aaa 1809 Leu Ser Ile Lys Pro Leu Gly Ala Ile Ser Pro Val Leu Asn Arg Lys 530 535 540 tta gct gta gga agt cac cca cta cca ccg aaa att cag tcc aaa gat 1857 Leu Ala Val Gly Ser His Pro Leu Pro Pro Lys Ile Gln Ser Lys Asp 545 550 555 560 gga aat aaa cct cca ccc cta aaa act tct gag ata aca gac cca gca 1905 Gly Asn Lys Pro Pro Pro Leu Lys Thr Ser Glu Ile Thr Asp Pro Ala 565 570 575 caa gtg tca aaa cca acc caa gga tct gct ttc aaa cca cct gtg cca 1953 Gln Val Ser Lys Pro Thr Gln Gly Ser Ala Phe Lys Pro Pro Val Pro 580 585 590 cca cga cca caa gcg aaa gtt cct ttg cct tcc gcc gat gct cca aat 2001 Pro Arg Pro Gln Ala Lys Val Pro Leu Pro Ser Ala Asp Ala Pro Asn 595 600 605 cag gca gaa cca gat gtt ctc gtt gaa aag cca gag aag gtg gtg cca 2049 Gln Ala Glu Pro Asp Val Leu Val Glu Lys Pro Glu Lys Val Val Pro 610 615 620 cct cct ctt gta gat aaa tct gct gaa aag caa gca aaa aat gtg gat 2097 Pro Pro Leu Val Asp Lys Ser Ala Glu Lys Gln Ala Lys Asn Val Asp 625 630 635 640 gcc ata gac gat gca gct gca cct aag caa ttt tta gca aag caa gaa 2145 Ala Ile Asp Asp Ala Ala Ala Pro Lys Gln Phe Leu Ala Lys Gln Glu 645 650 655 gtg gcc aaa gat gtc act tca gaa act tcc tgc cct act aag gac agt 2193 Val Ala Lys Asp Val Thr Ser Glu Thr Ser Cys Pro Thr Lys Asp Ser 660 665 670 tcg gac gac cgt caa aca tgg gaa tca tca gaa att ctt tat cgt aat 2241 Ser Asp Asp Arg Gln Thr Trp Glu Ser Ser Glu Ile Leu Tyr Arg Asn 675 680 685 aag cta gga aaa tgg aca aga acc aga gca tcc tgt ttg ttt gac ata 2289 Lys Leu Gly Lys Trp Thr Arg Thr Arg Ala Ser Cys Leu Phe Asp Ile 690 695 700 gaa gcc tgt cac agg tac tta aac att gca ttg tgg tgc agg gat cct 2337 Glu Ala Cys His Arg Tyr Leu Asn Ile Ala Leu Trp Cys Arg Asp Pro 705 710 715 720 ttc aag ttg gga ggt ctc atc tgt ttg ggg cat gtt agt tta aaa ctt 2385 Phe Lys Leu Gly Gly Leu Ile Cys Leu Gly His Val Ser Leu Lys Leu 725 730 735 gaa gat gtg gct tta gga tgc cta gct aca tca aac acg gaa tac ctt 2433 Glu Asp Val Ala Leu Gly Cys Leu Ala Thr Ser Asn Thr Glu Tyr Leu 740 745 750 tcc aaa ttg aga ctg gaa gcc ccc tca cct aag gct ata gtc act aga 2481 Ser Lys Leu Arg Leu Glu Ala Pro Ser Pro Lys Ala Ile Val Thr Arg 755 760 765 acc gca cta cgc aat ctg agt atg caa aag gga ttc aat gac aaa ttt 2529 Thr Ala Leu Arg Asn Leu Ser Met Gln Lys Gly Phe Asn Asp Lys Phe 770 775 780 tgc tat ggt gac att act att cac ttc aaa tat ttg aaa gaa gga gaa 2577 Cys Tyr Gly Asp Ile Thr Ile His Phe Lys Tyr Leu Lys Glu Gly Glu 785 790 795 800 tca gac cac cat gta gtt act aac gta gaa aaa gaa aaa gaa ccc cat 2625 Ser Asp His His Val Val Thr Asn Val Glu Lys Glu Lys Glu Pro His 805 810 815 ttg gtt gaa gaa gtt tct gtt ctc cct aaa gag gag caa ttt gtt gga 2673 Leu Val Glu Glu Val Ser Val Leu Pro Lys Glu Glu Gln Phe Val Gly 820 825 830 cag atg ggt tta aca gaa aac aaa cac agt ttt cag gat act cag ttc 2721 Gln Met Gly Leu Thr Glu Asn Lys His Ser Phe Gln Asp Thr Gln Phe 835 840 845 cag aac cca aca tgg tgt gac tac tgt aag aaa aaa gtt tgg act aaa 2769 Gln Asn Pro Thr Trp Cys Asp Tyr Cys Lys Lys Lys Val Trp Thr Lys 850 855 860 gca gct tcc cag tgt atg ttt tgt gct tat gtt tgc cat aaa aaa tgt 2817 Ala Ala Ser Gln Cys Met Phe Cys Ala Tyr Val Cys His Lys Lys Cys 865 870 875 880 caa gaa aag tgt cta gct gag act tct gtt tgt gga gca act gat agg 2865 Gln Glu Lys Cys Leu Ala Glu Thr Ser Val Cys Gly Ala Thr Asp Arg 885 890 895 cga ata gac agg aca ctg aaa aac ctt agg ctg gaa gga cag gaa acc 2913 Arg Ile Asp Arg Thr Leu Lys Asn Leu Arg Leu Glu Gly Gln Glu Thr 900 905 910 ctc tta ggc ctg cct cct cgt gtt gat gct gaa gct agc aag tca gtc 2961 Leu Leu Gly Leu Pro Pro Arg Val Asp Ala Glu Ala Ser Lys Ser Val 915 920 925 aat aaa aca aca ggt ttg aca agg cat att atc aat act agt tct cgt 3009 Asn Lys Thr Thr Gly Leu Thr Arg His Ile Ile Asn Thr Ser Ser Arg 930 935 940 tta tta aat ttg cgt caa gtc tct aaa act cgc ctt tct gaa cca gga 3057 Leu Leu Asn Leu Arg Gln Val Ser Lys Thr Arg Leu Ser Glu Pro Gly 945 950 955 960 acc gat ctc gta gaa cct tca cca aaa cac aca ccc aac acg tca gac 3105 Thr Asp Leu Val Glu Pro Ser Pro Lys His Thr Pro Asn Thr Ser Asp 965 970 975 aac gaa ggc agt gac acg gag gtc tgt ggt cca aac agt cct tct aaa 3153 Asn Glu Gly Ser Asp Thr Glu Val Cys Gly Pro Asn Ser Pro Ser Lys 980 985 990 cgg gga aac agc aca gga ata aag tta gtg aga aaa gag ggt ggt ctg 3201 Arg Gly Asn Ser Thr Gly Ile Lys Leu Val Arg Lys Glu Gly Gly Leu 995 1000 1005 gat gac agt gtt ttc att gca gtt aaa gaa att ggt cgt gat ctg tac 3249 Asp Asp Ser Val Phe Ile Ala Val Lys Glu Ile Gly Arg Asp Leu Tyr 1010 1015 1020 agg ggc ttg cct aca gag gaa agg atc cag aaa cta gag ttc atg ttg 3297 Arg Gly Leu Pro Thr Glu Glu Arg Ile Gln Lys Leu Glu Phe Met Leu 1025 1030 1035 1040 gat aag cta cag aat gaa att gat cag gag ttg gaa cac aat aat tcc 3345 Asp Lys Leu Gln Asn Glu Ile Asp Gln Glu Leu Glu His Asn Asn Ser 1045 1050 1055 ctt gtt aga gaa gaa aaa gag aca act gat aca agg aaa aaa tca ctt 3393 Leu Val Arg Glu Glu Lys Glu Thr Thr Asp Thr Arg Lys Lys Ser Leu 1060 1065 1070 ctt tct gct gcc tta gct aaa tca ggt gaa agg cta caa gct cta aca 3441 Leu Ser Ala Ala Leu Ala Lys Ser Gly Glu Arg Leu Gln Ala Leu Thr 1075 1080 1085 ctt ctt atg att cac tac aga gca ggc att gaa gat ata gaa act tta 3489 Leu Leu Met Ile His Tyr Arg Ala Gly Ile Glu Asp Ile Glu Thr Leu 1090 1095 1100 gaa agt ctg tct tta gac cag cac tcc aaa aaa ata agc aag tac aca 3537 Glu Ser Leu Ser Leu Asp Gln His Ser Lys Lys Ile Ser Lys Tyr Thr 1105 1110 1115 1120 gat gat aca gaa gaa gac ctt gat aat gaa ata agc caa cta ata gac 3585 Asp Asp Thr Glu Glu Asp Leu Asp Asn Glu Ile Ser Gln Leu Ile Asp 1125 1130 1135 tct cag cca ttc agc agc ata tca gat gac tta ttt ggc cca tcc gag 3633 Ser Gln Pro Phe Ser Ser Ile Ser Asp Asp Leu Phe Gly Pro Ser Glu 1140 1145 1150 tct gtg tagcagacag gtctatttaa actttcaaat gaacagggta aagttgcatc 3689 Ser Val taaagtacca cagatacaac catgtttaaa tcctcgtatg cactctggcc tgcttctcca 3749 gttacttgct tgtgtaagaa caaaaatgag aaaggttgtt ttccagtaaa aacatgacca 3809 gcttactaat tggttgtttt ggattgcatt tatagctatg cttttttggg tttatactgg 3869 gaatttattt ttactaaatt atttaacttt tctaattatg taattatgta agctagcttt 3929 tcatgtttat gtatgtatgg tgtccccttg tgttattttt cttcctcttg gtttttgaat 3989 tagtgttaaa tagaatactg tctggattct taaaatattt tcatttccat catggttata 4049 acaaatttgc tgcatgccca aactgacaac agcaatcact gagggaacag gttttgaatc 4109 tttcttttgt gttatgaagt ttatcgtctc tacttgcttg agatttttgt tattttgggg 4169 gtttgggggt gctttttgtt ttgtttttgc caaatgtaac atgaaagcag atgctgcagc 4229 tttagtctgt tatgctgatt tagtaaaaaa aaatttttta catatattgc ttgctttcga 4289 tgcttctgtg aaattttttt ctaaagcttt tgtgcagctg tatggtaaaa atatggtgat 4349 taatttgaag agcttacatt gaaagacaat gtaataggaa ataaatgtag attgcagttg 4409 gtcaagaatt ttgtagagag gataacaaga cttaattact gaaaaacagt aacatagcat 4469 tttgaaatat gatcttttaa aatattgatg ctttcctttt aaatggaaat ttaaatttta 4529 taattaaaag tttaaacatt tatgataatt ttcctcatca gttctcccat aggaaataaa 4589 gcatgtgaaa gggtatttaa agttttggag gactcttttt aaaatgactg tgttgataac 4649 tagtttgggc tggttttgtt ttagaaaaaa cattttcatg taggagtatt ctgtgaagga 4709 aaggaatcat gcaaaatata ctttttgctt tggcgtctta cagttgtaaa ggaatggtga 4769 tcattctgaa tacttctgta gtgagtattc at 4801 26 1154 PRT Homo sapiens 26 Met Gly Leu Leu Leu Met Ile Leu Ala Ser Ala Val Leu Gly Ser Phe 1 5 10 15 Leu Thr Leu Leu Ala Gln Phe Phe Leu Leu Tyr Arg Arg Gln Pro Glu 20 25 30 Pro Pro Ala Asp Glu Ala Ala Arg Ala Gly Glu Gly Phe Arg Tyr Ile 35 40 45 Lys Pro Val Pro Gly Leu Leu Leu Arg Glu Tyr Leu Tyr Gly Gly Gly 50 55 60 Arg Asp Glu Glu Pro Ser Gly Ala Ala Pro Glu Gly Gly Ala Thr Pro 65 70 75 80 Thr Ala Ala Pro Glu Thr Pro Ala Pro Pro Thr Arg Glu Thr Cys Tyr 85 90 95 Phe Leu Asn Ala Thr Ile Leu Phe Leu Phe Arg Glu Leu Arg Asp Thr 100 105 110 Ala Leu Thr Arg Arg Trp Val Thr Lys Lys Ile Lys Val Glu Phe Glu 115 120 125 Glu Leu Leu Gln Thr Lys Thr Ala Gly Arg Leu Leu Glu Gly Leu Ser 130 135 140 Leu Arg Asp Val Phe Leu Gly Glu Thr Val Pro Phe Ile Lys Thr Ile 145 150 155 160 Arg Leu Val Arg Pro Val Val Pro Ser Ala Thr Gly Glu Pro Asp Gly 165 170 175 Pro Glu Gly Glu Ala Leu Pro Ala Ala Cys Pro Glu Glu Leu Ala Phe 180 185 190 Glu Ala Glu Val Glu Tyr Asn Gly Gly Phe His Leu Ala Ile Asp Val 195 200 205 Asp Leu Val Phe Gly Lys Ser Ala Tyr Leu Phe Val Lys Leu Ser Arg 210 215 220 Val Val Gly Arg Leu Arg Leu Val Phe Thr Arg Val Pro Phe Thr His 225 230 235 240 Trp Phe Phe Ser Phe Val Glu Asp Pro Leu Ile Asp Phe Glu Val Arg 245 250 255 Ser Gln Phe Glu Gly Arg Pro Met Pro Gln Leu Thr Ser Ile Ile Val 260 265 270 Asn Gln Leu Lys Lys Ile Ile Lys Arg Lys His Thr Leu Pro Asn Tyr 275 280 285 Lys Ile Arg Phe Lys Pro Phe Phe Pro Tyr Gln Thr Leu Gln Gly Phe 290 295 300 Glu Glu Asp Glu Glu His Ile His Ile Gln Gln Trp Ala Leu Thr Glu 305 310 315 320 Gly Arg Leu Lys Val Thr Leu Leu Glu Cys Ser Arg Leu Leu Ile Phe 325 330 335 Gly Ser Tyr Asp Arg Glu Ala Asn Val His Cys Thr Leu Glu Leu Ser 340 345 350 Ser Ser Val Trp Glu Glu Lys Gln Arg Ser Ser Ile Lys Thr Val Glu 355 360 365 Leu Ile Lys Gly Asn Leu Gln Ser Val Gly Leu Thr Leu Arg Leu Val 370 375 380 Gln Ser Thr Asp Gly Tyr Ala Gly His Val Ile Ile Glu Thr Val Ala 385 390 395 400 Pro Asn Ser Pro Ala Ala Ile Ala Asp Leu Gln Arg Gly Asp Arg Leu 405 410 415 Ile Ala Ile Gly Gly Val Lys Ile Thr Ser Thr Leu Gln Val Leu Lys 420 425 430 Leu Ile Lys Gln Ala Gly Asp Arg Val Leu Val Tyr Tyr Glu Arg Pro 435 440 445 Val Gly Gln Ser Asn Gln Gly Ala Val Leu Gln Asp Asn Phe Gly Gln 450 455 460 Leu Glu Glu Asn Phe Leu Ser Ser Ser Cys Gln Ser Gly Tyr Glu Glu 465 470 475 480 Glu Ala Ala Gly Leu Thr Val Asp Thr Glu Ser Arg Glu Leu Asp Ser 485 490 495 Glu Phe Glu Asp Leu Ala Ser Asp Val Arg Ala Gln Asn Glu Phe Lys 500 505 510 Asp Glu Ala Gln Ser Leu Ser His Ser Pro Lys Arg Val Pro Thr Thr 515 520 525 Leu Ser Ile Lys Pro Leu Gly Ala Ile Ser Pro Val Leu Asn Arg Lys 530 535 540 Leu Ala Val Gly Ser His Pro Leu Pro Pro Lys Ile Gln Ser Lys Asp 545 550 555 560 Gly Asn Lys Pro Pro Pro Leu Lys Thr Ser Glu Ile Thr Asp Pro Ala 565 570 575 Gln Val Ser Lys Pro Thr Gln Gly Ser Ala Phe Lys Pro Pro Val Pro 580 585 590 Pro Arg Pro Gln Ala Lys Val Pro Leu Pro Ser Ala Asp Ala Pro Asn 595 600 605 Gln Ala Glu Pro Asp Val Leu Val Glu Lys Pro Glu Lys Val Val Pro 610 615 620 Pro Pro Leu Val Asp Lys Ser Ala Glu Lys Gln Ala Lys Asn Val Asp 625 630 635 640 Ala Ile Asp Asp Ala Ala Ala Pro Lys Gln Phe Leu Ala Lys Gln Glu 645 650 655 Val Ala Lys Asp Val Thr Ser Glu Thr Ser Cys Pro Thr Lys Asp Ser 660 665 670 Ser Asp Asp Arg Gln Thr Trp Glu Ser Ser Glu Ile Leu Tyr Arg Asn 675 680 685 Lys Leu Gly Lys Trp Thr Arg Thr Arg Ala Ser Cys Leu Phe Asp Ile 690 695 700 Glu Ala Cys His Arg Tyr Leu Asn Ile Ala Leu Trp Cys Arg Asp Pro 705 710 715 720 Phe Lys Leu Gly Gly Leu Ile Cys Leu Gly His Val Ser Leu Lys Leu 725 730 735 Glu Asp Val Ala Leu Gly Cys Leu Ala Thr Ser Asn Thr Glu Tyr Leu 740 745 750 Ser Lys Leu Arg Leu Glu Ala Pro Ser Pro Lys Ala Ile Val Thr Arg 755 760 765 Thr Ala Leu Arg Asn Leu Ser Met Gln Lys Gly Phe Asn Asp Lys Phe 770 775 780 Cys Tyr Gly Asp Ile Thr Ile His Phe Lys Tyr Leu Lys Glu Gly Glu 785 790 795 800 Ser Asp His His Val Val Thr Asn Val Glu Lys Glu Lys Glu Pro His 805 810 815 Leu Val Glu Glu Val Ser Val Leu Pro Lys Glu Glu Gln Phe Val Gly 820 825 830 Gln Met Gly Leu Thr Glu Asn Lys His Ser Phe Gln Asp Thr Gln Phe 835 840 845 Gln Asn Pro Thr Trp Cys Asp Tyr Cys Lys Lys Lys Val Trp Thr Lys 850 855 860 Ala Ala Ser Gln Cys Met Phe Cys Ala Tyr Val Cys His Lys Lys Cys 865 870 875 880 Gln Glu Lys Cys Leu Ala Glu Thr Ser Val Cys Gly Ala Thr Asp Arg 885 890 895 Arg Ile Asp Arg Thr Leu Lys Asn Leu Arg Leu Glu Gly Gln Glu Thr 900 905 910 Leu Leu Gly Leu Pro Pro Arg Val Asp Ala Glu Ala Ser Lys Ser Val 915 920 925 Asn Lys Thr Thr Gly Leu Thr Arg His Ile Ile Asn Thr Ser Ser Arg 930 935 940 Leu Leu Asn Leu Arg Gln Val Ser Lys Thr Arg Leu Ser Glu Pro Gly 945 950 955 960 Thr Asp Leu Val Glu Pro Ser Pro Lys His Thr Pro Asn Thr Ser Asp 965 970 975 Asn Glu Gly Ser Asp Thr Glu Val Cys Gly Pro Asn Ser Pro Ser Lys 980 985 990 Arg Gly Asn Ser Thr Gly Ile Lys Leu Val Arg Lys Glu Gly Gly Leu 995 1000 1005 Asp Asp Ser Val Phe Ile Ala Val Lys Glu Ile Gly Arg Asp Leu Tyr 1010 1015 1020 Arg Gly Leu Pro Thr Glu Glu Arg Ile Gln Lys Leu Glu Phe Met Leu 1025 1030 1035 1040 Asp Lys Leu Gln Asn Glu Ile Asp Gln Glu Leu Glu His Asn Asn Ser 1045 1050 1055 Leu Val Arg Glu Glu Lys Glu Thr Thr Asp Thr Arg Lys Lys Ser Leu 1060 1065 1070 Leu Ser Ala Ala Leu Ala Lys Ser Gly Glu Arg Leu Gln Ala Leu Thr 1075 1080 1085 Leu Leu Met Ile His Tyr Arg Ala Gly Ile Glu Asp Ile Glu Thr Leu 1090 1095 1100 Glu Ser Leu Ser Leu Asp Gln His Ser Lys Lys Ile Ser Lys Tyr Thr 1105 1110 1115 1120 Asp Asp Thr Glu Glu Asp Leu Asp Asn Glu Ile Ser Gln Leu Ile Asp 1125 1130 1135 Ser Gln Pro Phe Ser Ser Ile Ser Asp Asp Leu Phe Gly Pro Ser Glu 1140 1145 1150 Ser Val 27 1157 DNA Homo sapiens CDS (23)..(1108) 27 cttcggcctg tcggttttca cc atg gag cag ctg agc tca gca aac acc cgc 52 Met Glu Gln Leu Ser Ser Ala Asn Thr Arg 1 5 10 ttc gcc ttg gac ctg ttc ctg gcg ttg agt gag aac aat ccg gct gga 100 Phe Ala Leu Asp Leu Phe Leu Ala Leu Ser Glu Asn Asn Pro Ala Gly 15 20 25 aac atc ttc atc tct ccc ttc agc att tca tct gct atg gcc atg gtt 148 Asn Ile Phe Ile Ser Pro Phe Ser Ile Ser Ser Ala Met Ala Met Val 30 35 40 ttt ctg ggg acc aga ggt aac acg gca gca cag ctg tcc aag act ttc 196 Phe Leu Gly Thr Arg Gly Asn Thr Ala Ala Gln Leu Ser Lys Thr Phe 45 50 55 cat ttc aac acg gtt gaa gag gtt cat tca aga ttc cag agt ctg aat 244 His Phe Asn Thr Val Glu Glu Val His Ser Arg Phe Gln Ser Leu Asn 60 65 70 gct gat atc aac aaa cgt gga gcg tct tat att ctg aaa ctt gct aat 292 Ala Asp Ile Asn Lys Arg Gly Ala Ser Tyr Ile Leu Lys Leu Ala Asn 75 80 85 90 aga tta tat gga gag aaa act tac aat ttc ctt cct gag ttc ttg gtt 340 Arg Leu Tyr Gly Glu Lys Thr Tyr Asn Phe Leu Pro Glu Phe Leu Val 95 100 105 tcg act cag aaa aca tat ggt gct gac ctg gcc agt gtg gat ttt cag 388 Ser Thr Gln Lys Thr Tyr Gly Ala Asp Leu Ala Ser Val Asp Phe Gln 110 115 120 cat gcc tct gaa gat gca agg aag acc ata aac cag tgg gtt gat aac 436 His Ala Ser Glu Asp Ala Arg Lys Thr Ile Asn Gln Trp Val Asp Asn 125 130 135 atg acc aaa ctt gtg cta gta aat gcc atc tat ttc aag gga aac tgg 484 Met Thr Lys Leu Val Leu Val Asn Ala Ile Tyr Phe Lys Gly Asn Trp 140 145 150 aag gat aaa ttc atg aaa gaa gcc acg acg aat gca cca ttc aga ttg 532 Lys Asp Lys Phe Met Lys Glu Ala Thr Thr Asn Ala Pro Phe Arg Leu 155 160 165 170 aat aag aaa gac aga aaa act gtg aaa atg atg tat cag aag aaa aaa 580 Asn Lys Lys Asp Arg Lys Thr Val Lys Met Met Tyr Gln Lys Lys Lys 175 180 185 ttt gca tat ggc tac atc gag gac ctt aag tgc cgt gtg ctg gaa ctg 628 Phe Ala Tyr Gly Tyr Ile Glu Asp Leu Lys Cys Arg Val Leu Glu Leu 190 195 200 cct tac caa ggc gag gag ctc agc atg gtc atc ctg ctg ccg gat gac 676 Pro Tyr Gln Gly Glu Glu Leu Ser Met Val Ile Leu Leu Pro Asp Asp 205 210 215 att gag gac gag tcc acg ggc ctg aag aag att gag gaa cag ttg act 724 Ile Glu Asp Glu Ser Thr Gly Leu Lys Lys Ile Glu Glu Gln Leu Thr 220 225 230 ttg gaa aag ttg cat gag tgg act aaa cct gag aat ctc gat ttc att 772 Leu Glu Lys Leu His Glu Trp Thr Lys Pro Glu Asn Leu Asp Phe Ile 235 240 245 250 gaa gtt aat gtc agc ttg ccc agg ttc aaa ctg gaa gag agt tac act 820 Glu Val Asn Val Ser Leu Pro Arg Phe Lys Leu Glu Glu Ser Tyr Thr 255 260 265 ctc aac tcc gac ctc gcc cgc cta ggt gtg cag gat ctc ttt aac agt 868 Leu Asn Ser Asp Leu Ala Arg Leu Gly Val Gln Asp Leu Phe Asn Ser 270 275 280 agc aag gct gat ctg tct ggc atg tca gga gcc aga gat att ttt ata 916 Ser Lys Ala Asp Leu Ser Gly Met Ser Gly Ala Arg Asp Ile Phe Ile 285 290 295 tca aaa att gtc cac aag tca ttt gtg gaa gtg aat gaa gag gga aca 964 Ser Lys Ile Val His Lys Ser Phe Val Glu Val Asn Glu Glu Gly Thr 300 305 310 gag gcg gca gct gcc aca gca ggc atc gca act ttc tgc atg ttg atg 1012 Glu Ala Ala Ala Ala Thr Ala Gly Ile Ala Thr Phe Cys Met Leu Met 315 320 325 330 ccc gaa gaa aat ttc act gcc gac cat cca ttc ctt ttc ttt att cgg 1060 Pro Glu Glu Asn Phe Thr Ala Asp His Pro Phe Leu Phe Phe Ile Arg 335 340 345 cat aat tcc tca ggt agc atc cta ttc ttg ggg aga ttt tct tcc cct 1108 His Asn Ser Ser Gly Ser Ile Leu Phe Leu Gly Arg Phe Ser Ser Pro 350 355 360 tagaagaaag agactgtagc aatacaaaaa tcaagcttag tgctaaggg 1157 28 362 PRT Homo sapiens 28 Met Glu Gln Leu Ser Ser Ala Asn Thr Arg Phe Ala Leu Asp Leu Phe 1 5 10 15 Leu Ala Leu Ser Glu Asn Asn Pro Ala Gly Asn Ile Phe Ile Ser Pro 20 25 30 Phe Ser Ile Ser Ser Ala Met Ala Met Val Phe Leu Gly Thr Arg Gly 35 40 45 Asn Thr Ala Ala Gln Leu Ser Lys Thr Phe His Phe Asn Thr Val Glu 50 55 60 Glu Val His Ser Arg Phe Gln Ser Leu Asn Ala Asp Ile Asn Lys Arg 65 70 75 80 Gly Ala Ser Tyr Ile Leu Lys Leu Ala Asn Arg Leu Tyr Gly Glu Lys 85 90 95 Thr Tyr Asn Phe Leu Pro Glu Phe Leu Val Ser Thr Gln Lys Thr Tyr 100 105 110 Gly Ala Asp Leu Ala Ser Val Asp Phe Gln His Ala Ser Glu Asp Ala 115 120 125 Arg Lys Thr Ile Asn Gln Trp Val Asp Asn Met Thr Lys Leu Val Leu 130 135 140 Val Asn Ala Ile Tyr Phe Lys Gly Asn Trp Lys Asp Lys Phe Met Lys 145 150 155 160 Glu Ala Thr Thr Asn Ala Pro Phe Arg Leu Asn Lys Lys Asp Arg Lys 165 170 175 Thr Val Lys Met Met Tyr Gln Lys Lys Lys Phe Ala Tyr Gly Tyr Ile 180 185 190 Glu Asp Leu Lys Cys Arg Val Leu Glu Leu Pro Tyr Gln Gly Glu Glu 195 200 205 Leu Ser Met Val Ile Leu Leu Pro Asp Asp Ile Glu Asp Glu Ser Thr 210 215 220 Gly Leu Lys Lys Ile Glu Glu Gln Leu Thr Leu Glu Lys Leu His Glu 225 230 235 240 Trp Thr Lys Pro Glu Asn Leu Asp Phe Ile Glu Val Asn Val Ser Leu 245 250 255 Pro Arg Phe Lys Leu Glu Glu Ser Tyr Thr Leu Asn Ser Asp Leu Ala 260 265 270 Arg Leu Gly Val Gln Asp Leu Phe Asn Ser Ser Lys Ala Asp Leu Ser 275 280 285 Gly Met Ser Gly Ala Arg Asp Ile Phe Ile Ser Lys Ile Val His Lys 290 295 300 Ser Phe Val Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr 305 310 315 320 Ala Gly Ile Ala Thr Phe Cys Met Leu Met Pro Glu Glu Asn Phe Thr 325 330 335 Ala Asp His Pro Phe Leu Phe Phe Ile Arg His Asn Ser Ser Gly Ser 340 345 350 Ile Leu Phe Leu Gly Arg Phe Ser Ser Pro 355 360 29 1550 DNA Homo sapiens CDS (283)..(1419) 29 cggcggcctg tcggagctgt ttgtgacggt ttccaggcag cccagggcca ggccgcggct 60 cctatctgca gctgcaggga gagagaggag gaaccccgtg cgattctaga gacgatttca 120 caacaaggag aaatcagctt tgtgcttaca tgccgagcag ccagcacggt tcttctttgc 180 ctgtcctcgg gggaaatcag ggctctgaga gtggagatcg agatgggcta gtgggtggcg 240 gatgggacgc tgcacggcca gaccctggac tgtgttttca cc atg gag cag ctg 294 Met Glu Gln Leu 1 agc tca gca aac acc cgc ttc gcc ttg gac ctg ttc ctg gcg ttg agt 342 Ser Ser Ala Asn Thr Arg Phe Ala Leu Asp Leu Phe Leu Ala Leu Ser 5 10 15 20 gag aac aat ccg gct gga aac atc ttc atc tct ccc ttc agc att tca 390 Glu Asn Asn Pro Ala Gly Asn Ile Phe Ile Ser Pro Phe Ser Ile Ser 25 30 35 tct gct atg gcc atg gtt ttt ctg ggg acc aga ggt aac acg gca gca 438 Ser Ala Met Ala Met Val Phe Leu Gly Thr Arg Gly Asn Thr Ala Ala 40 45 50 cag ctg tcc aag act ttc cat ttc aac acg gtt gaa gag gtt cat tca 486 Gln Leu Ser Lys Thr Phe His Phe Asn Thr Val Glu Glu Val His Ser 55 60 65 aga ttc cag agt ctg aat gct gat atc aac aaa cgt gga gcg tct tat 534 Arg Phe Gln Ser Leu Asn Ala Asp Ile Asn Lys Arg Gly Ala Ser Tyr 70 75 80 att ctg aaa ctt gct aat aga tta tat gga gag aaa act tac aat ttc 582 Ile Leu Lys Leu Ala Asn Arg Leu Tyr Gly Glu Lys Thr Tyr Asn Phe 85 90 95 100 ctt cct gag ttc ttg gtt tcg act cag aaa aca tat ggt gct gac ctg 630 Leu Pro Glu Phe Leu Val Ser Thr Gln Lys Thr Tyr Gly Ala Asp Leu 105 110 115 gcc agt gtg gat ttt cag cat gcc tct gaa gat gca agg aag acc ata 678 Ala Ser Val Asp Phe Gln His Ala Ser Glu Asp Ala Arg Lys Thr Ile 120 125 130 aac cag tgg gtc aaa gga cag aca gaa gga aaa att ccg gaa ctg ttg 726 Asn Gln Trp Val Lys Gly Gln Thr Glu Gly Lys Ile Pro Glu Leu Leu 135 140 145 gct tcg ggc atg gtt gat aac atg acc aaa ctt gtg cta gta aat gcc 774 Ala Ser Gly Met Val Asp Asn Met Thr Lys Leu Val Leu Val Asn Ala 150 155 160 atc tat ttc aag gga aac tgg aag gat aaa ttc atg aaa gaa gcc acg 822 Ile Tyr Phe Lys Gly Asn Trp Lys Asp Lys Phe Met Lys Glu Ala Thr 165 170 175 180 acg aat gca cca ttc aga ttg aat aag aaa gac aga aaa act gtg aaa 870 Thr Asn Ala Pro Phe Arg Leu Asn Lys Lys Asp Arg Lys Thr Val Lys 185 190 195 atg atg tat cag aag aaa aaa ttt gca tat ggc tac atc gag gac ctt 918 Met Met Tyr Gln Lys Lys Lys Phe Ala Tyr Gly Tyr Ile Glu Asp Leu 200 205 210 aag tgc cgt gtg ctg gaa ctg cct tac caa ggc gag gag ctc agc atg 966 Lys Cys Arg Val Leu Glu Leu Pro Tyr Gln Gly Glu Glu Leu Ser Met 215 220 225 gtc atc ctg ctg ccg gat gac att gag gac gag tcc acg ggc ctg aag 1014 Val Ile Leu Leu Pro Asp Asp Ile Glu Asp Glu Ser Thr Gly Leu Lys 230 235 240 aag att gag gaa cag ttg act ttg gaa aag ttg cat gag tgg act aaa 1062 Lys Ile Glu Glu Gln Leu Thr Leu Glu Lys Leu His Glu Trp Thr Lys 245 250 255 260 cct gag aat ctc gat ttc att gaa gtt aat gtc agc ttg ccc agg ttc 1110 Pro Glu Asn Leu Asp Phe Ile Glu Val Asn Val Ser Leu Pro Arg Phe 265 270 275 aaa ctg gaa gag agt tac act ctc aac tcc gac ctc gcc cgc cta ggt 1158 Lys Leu Glu Glu Ser Tyr Thr Leu Asn Ser Asp Leu Ala Arg Leu Gly 280 285 290 gtg cag gat ctc ttt aac agt agc aag gct gat ctg tct ggc atg tca 1206 Val Gln Asp Leu Phe Asn Ser Ser Lys Ala Asp Leu Ser Gly Met Ser 295 300 305 gga gcc aga gat att ttt ata tca aaa att gtc cac aag tca ttt gtg 1254 Gly Ala Arg Asp Ile Phe Ile Ser Lys Ile Val His Lys Ser Phe Val 310 315 320 gaa gtg aat gaa gag gga aca gag gcg gca gct gcc aca gca ggc atc 1302 Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala Thr Ala Gly Ile 325 330 335 340 gca act ttc tgc atg ttg atg ccc gaa gaa aat ttc act gcc gac cat 1350 Ala Thr Phe Cys Met Leu Met Pro Glu Glu Asn Phe Thr Ala Asp His 345 350 355 cca ttc ctt ttc ttt att cgg cat aat tcc tca ggt agc atc cta ttc 1398 Pro Phe Leu Phe Phe Ile Arg His Asn Ser Ser Gly Ser Ile Leu Phe 360 365 370 ttg ggg aga ttt tct tcc cct tagaagaaag agactgtagc aatacaaaaa 1449 Leu Gly Arg Phe Ser Ser Pro 375 tcaagcttag tgctttatta cctgagtttt taatagagcc aatatgtctt atatctttac 1509 caataaaacc actgtccaga aacaaaaaaa aaaaaaaaaa a 1550 30 379 PRT Homo sapiens 30 Met Glu Gln Leu Ser Ser Ala Asn Thr Arg Phe Ala Leu Asp Leu Phe 1 5 10 15 Leu Ala Leu Ser Glu Asn Asn Pro Ala Gly Asn Ile Phe Ile Ser Pro 20 25 30 Phe Ser Ile Ser Ser Ala Met Ala Met Val Phe Leu Gly Thr Arg Gly 35 40 45 Asn Thr Ala Ala Gln Leu Ser Lys Thr Phe His Phe Asn Thr Val Glu 50 55 60 Glu Val His Ser Arg Phe Gln Ser Leu Asn Ala Asp Ile Asn Lys Arg 65 70 75 80 Gly Ala Ser Tyr Ile Leu Lys Leu Ala Asn Arg Leu Tyr Gly Glu Lys 85 90 95 Thr Tyr Asn Phe Leu Pro Glu Phe Leu Val Ser Thr Gln Lys Thr Tyr 100 105 110 Gly Ala Asp Leu Ala Ser Val Asp Phe Gln His Ala Ser Glu Asp Ala 115 120 125 Arg Lys Thr Ile Asn Gln Trp Val Lys Gly Gln Thr Glu Gly Lys Ile 130 135 140 Pro Glu Leu Leu Ala Ser Gly Met Val Asp Asn Met Thr Lys Leu Val 145 150 155 160 Leu Val Asn Ala Ile Tyr Phe Lys Gly Asn Trp Lys Asp Lys Phe Met 165 170 175 Lys Glu Ala Thr Thr Asn Ala Pro Phe Arg Leu Asn Lys Lys Asp Arg 180 185 190 Lys Thr Val Lys Met Met Tyr Gln Lys Lys Lys Phe Ala Tyr Gly Tyr 195 200 205 Ile Glu Asp Leu Lys Cys Arg Val Leu Glu Leu Pro Tyr Gln Gly Glu 210 215 220 Glu Leu Ser Met Val Ile Leu Leu Pro Asp Asp Ile Glu Asp Glu Ser 225 230 235 240 Thr Gly Leu Lys Lys Ile Glu Glu Gln Leu Thr Leu Glu Lys Leu His 245 250 255 Glu Trp Thr Lys Pro Glu Asn Leu Asp Phe Ile Glu Val Asn Val Ser 260 265 270 Leu Pro Arg Phe Lys Leu Glu Glu Ser Tyr Thr Leu Asn Ser Asp Leu 275 280 285 Ala Arg Leu Gly Val Gln Asp Leu Phe Asn Ser Ser Lys Ala Asp Leu 290 295 300 Ser Gly Met Ser Gly Ala Arg Asp Ile Phe Ile Ser Lys Ile Val His 305 310 315 320 Lys Ser Phe Val Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala 325 330 335 Thr Ala Gly Ile Ala Thr Phe Cys Met Leu Met Pro Glu Glu Asn Phe 340 345 350 Thr Ala Asp His Pro Phe Leu Phe Phe Ile Arg His Asn Ser Ser Gly 355 360 365 Ser Ile Leu Phe Leu Gly Arg Phe Ser Ser Pro 370 375 31 697 DNA Homo sapiens CDS (33)..(566) 31 cagtgtgctg gaattcgccc ttaaccggca gg atg tcg gag gtg cgg ctg cca 53 Met Ser Glu Val Arg Leu Pro 1 5 ccg cta cgc gcc ctg gac gac ttt gtt ctg ggg tcg gcg cgt ctg gcg 101 Pro Leu Arg Ala Leu Asp Asp Phe Val Leu Gly Ser Ala Arg Leu Ala 10 15 20 gct ccg gat cca tgc gac ccg cag cga tgg tgc cac cgc gtc atc aac 149 Ala Pro Asp Pro Cys Asp Pro Gln Arg Trp Cys His Arg Val Ile Asn 25 30 35 aac ctc ctc tac tac caa acc aac tac ctt ctc tgc ttc ggc atc ggc 197 Asn Leu Leu Tyr Tyr Gln Thr Asn Tyr Leu Leu Cys Phe Gly Ile Gly 40 45 50 55 ctc gct ctc gcc ggg tac gtg cgg cca ctt cat acg ctc ctg agc gcg 245 Leu Ala Leu Ala Gly Tyr Val Arg Pro Leu His Thr Leu Leu Ser Ala 60 65 70 ctg gta gtg gcg gtg gcc ctc ggc gtg ctg gtg tgg gca gct gag acc 293 Leu Val Val Ala Val Ala Leu Gly Val Leu Val Trp Ala Ala Glu Thr 75 80 85 cgc gca gct gtg cgc cgc tgc cgc cgc agc cac cct gca gcc tgc ctg 341 Arg Ala Ala Val Arg Arg Cys Arg Arg Ser His Pro Ala Ala Cys Leu 90 95 100 gcc gca gtg ctt gcc gtc ggc ctc ctg gtg ctc tgg gtc gcg ggc ggc 389 Ala Ala Val Leu Ala Val Gly Leu Leu Val Leu Trp Val Ala Gly Gly 105 110 115 gct tgc acc ttc ctg ttc agc atc gcc ggg ccg gtg ctt ctg atc ctg 437 Ala Cys Thr Phe Leu Phe Ser Ile Ala Gly Pro Val Leu Leu Ile Leu 120 125 130 135 gtg cac gcc tcg ttg cgc ctg cgc aac ctt aag aac aag att gag aac 485 Val His Ala Ser Leu Arg Leu Arg Asn Leu Lys Asn Lys Ile Glu Asn 140 145 150 aag atc gag agc att ggt ctc aag cgg acg cca atg ggc ctg cta cta 533 Lys Ile Glu Ser Ile Gly Leu Lys Arg Thr Pro Met Gly Leu Leu Leu 155 160 165 gag gca ctg gga caa gag cag gag gct gga tcc taggcccctg ggatctgtac 586 Glu Ala Leu Gly Gln Glu Gln Glu Ala Gly Ser 170 175 ccaggacctg gagaatacca ccccaccccc agcccataat tgggacccag agccctttcc 646 cagcacttaa aacaggagcc tagagccgcc tgcccaaaca aaaaagggcg a 697 32 178 PRT Homo sapiens 32 Met Ser Glu Val Arg Leu Pro Pro Leu Arg Ala Leu Asp Asp Phe Val 1 5 10 15 Leu Gly Ser Ala Arg Leu Ala Ala Pro Asp Pro Cys Asp Pro Gln Arg 20 25 30 Trp Cys His Arg Val Ile Asn Asn Leu Leu Tyr Tyr Gln Thr Asn Tyr 35 40 45 Leu Leu Cys Phe Gly Ile Gly Leu Ala Leu Ala Gly Tyr Val Arg Pro 50 55 60 Leu His Thr Leu Leu Ser Ala Leu Val Val Ala Val Ala Leu Gly Val 65 70 75 80 Leu Val Trp Ala Ala Glu Thr Arg Ala Ala Val Arg Arg Cys Arg Arg 85 90 95 Ser His Pro Ala Ala Cys Leu Ala Ala Val Leu Ala Val Gly Leu Leu 100 105 110 Val Leu Trp Val Ala Gly Gly Ala Cys Thr Phe Leu Phe Ser Ile Ala 115 120 125 Gly Pro Val Leu Leu Ile Leu Val His Ala Ser Leu Arg Leu Arg Asn 130 135 140 Leu Lys Asn Lys Ile Glu Asn Lys Ile Glu Ser Ile Gly Leu Lys Arg 145 150 155 160 Thr Pro Met Gly Leu Leu Leu Glu Ala Leu Gly Gln Glu Gln Glu Ala 165 170 175 Gly Ser 33 581 DNA Homo sapiens CDS (32)..(496) 33 gcagtgtgtg gaatcgccct taaccggcag g atg tcg gag gtg cgg ctg cca 52 Met Ser Glu Val Arg Leu Pro 1 5 ccg cta cgc gcc ctg gac gac ttt gtt ctg ggg tcg gcg cgt ctg gcg 100 Pro Leu Arg Ala Leu Asp Asp Phe Val Leu Gly Ser Ala Arg Leu Ala 10 15 20 gct ccg gat cca tgc gac ccg cag cga tgg tgc cac cgc gtc atc aac 148 Ala Pro Asp Pro Cys Asp Pro Gln Arg Trp Cys His Arg Val Ile Asn 25 30 35 aac ctc ctc tac tac caa acc aac tac ctt ctc tgc ttc ggc atc ggc 196 Asn Leu Leu Tyr Tyr Gln Thr Asn Tyr Leu Leu Cys Phe Gly Ile Gly 40 45 50 55 ctc gct ctc gcc ggg cac gtg cgg cca ctt cat acg ctc cta agc gcg 244 Leu Ala Leu Ala Gly His Val Arg Pro Leu His Thr Leu Leu Ser Ala 60 65 70 ctg gta gtg gcg gtg gcc ctc ggc gtg ctg gtg tgg gca gct gag acc 292 Leu Val Val Ala Val Ala Leu Gly Val Leu Val Trp Ala Ala Glu Thr 75 80 85 cgc gca gct gtg cgc cgc tgc cgc cgc agc cac cct gca gcc tgc ctg 340 Arg Ala Ala Val Arg Arg Cys Arg Arg Ser His Pro Ala Ala Cys Leu 90 95 100 gcc gca gtg ctt gcc gtc ggc ctc ctg gtg cac gcc tcg ttg cgc ctg 388 Ala Ala Val Leu Ala Val Gly Leu Leu Val His Ala Ser Leu Arg Leu 105 110 115 cgc aac ctt aag aac aag att gag aac aag atc gag agc att ggt ctc 436 Arg Asn Leu Lys Asn Lys Ile Glu Asn Lys Ile Glu Ser Ile Gly Leu 120 125 130 135 aag cgg acg cca atg ggc ctg cta cta gag gca ctg gga caa gag cag 484 Lys Arg Thr Pro Met Gly Leu Leu Leu Glu Ala Leu Gly Gln Glu Gln 140 145 150 gag gct gga tcc taggcccctg ggatctgtac ccaggacctg gagaatacca 536 Glu Ala Gly Ser 155 ccccaccccc agcccataat tgggacccag agccctttcc cagca 581 34 155 PRT Homo sapiens 34 Met Ser Glu Val Arg Leu Pro Pro Leu Arg Ala Leu Asp Asp Phe Val 1 5 10 15 Leu Gly Ser Ala Arg Leu Ala Ala Pro Asp Pro Cys Asp Pro Gln Arg 20 25 30 Trp Cys His Arg Val Ile Asn Asn Leu Leu Tyr Tyr Gln Thr Asn Tyr 35 40 45 Leu Leu Cys Phe Gly Ile Gly Leu Ala Leu Ala Gly His Val Arg Pro 50 55 60 Leu His Thr Leu Leu Ser Ala Leu Val Val Ala Val Ala Leu Gly Val 65 70 75 80 Leu Val Trp Ala Ala Glu Thr Arg Ala Ala Val Arg Arg Cys Arg Arg 85 90 95 Ser His Pro Ala Ala Cys Leu Ala Ala Val Leu Ala Val Gly Leu Leu 100 105 110 Val His Ala Ser Leu Arg Leu Arg Asn Leu Lys Asn Lys Ile Glu Asn 115 120 125 Lys Ile Glu Ser Ile Gly Leu Lys Arg Thr Pro Met Gly Leu Leu Leu 130 135 140 Glu Ala Leu Gly Gln Glu Gln Glu Ala Gly Ser 145 150 155 35 6240 DNA Homo sapiens CDS (100)..(4641) 35 ctttctgtct ctcgggaccc ttatttcttc gtcacggtgt ccaggaccat tttgaccctg 60 tcggccccgg cacccccccg ccgcacccca gccccgagc atg ggg acg gcg ctg 114 Met Gly Thr Ala Leu 1 5 ctc cag cgc ggg ggc tgt ttt ctt ctg tgc ctc tcg ctg ctg ctc ctg 162 Leu Gln Arg Gly Gly Cys Phe Leu Leu Cys Leu Ser Leu Leu Leu Leu 10 15 20 ggc tgc tgg gcg gag ctg ggc agc ggg ctg gag ttt ccg ggc gcc gag 210 Gly Cys Trp Ala Glu Leu Gly Ser Gly Leu Glu Phe Pro Gly Ala Glu 25 30 35 ggc caa tgg acg cgc ttc ccc aag tgg aac gcc tgc tgc gag agc gag 258 Gly Gln Trp Thr Arg Phe Pro Lys Trp Asn Ala Cys Cys Glu Ser Glu 40 45 50 atg agc ttc cag ctc aag act cgc agc gcc cgc ggc ctc gtg ctc tac 306 Met Ser Phe Gln Leu Lys Thr Arg Ser Ala Arg Gly Leu Val Leu Tyr 55 60 65 ttc gac gac gag ggc ttc tgc gac ttc ctg gag ctg att ctg acg cgc 354 Phe Asp Asp Glu Gly Phe Cys Asp Phe Leu Glu Leu Ile Leu Thr Arg 70 75 80 85 ggc ggc cgc ctg cag ctc agc ttc tcc atc ttc tgc gct gag cct gcg 402 Gly Gly Arg Leu Gln Leu Ser Phe Ser Ile Phe Cys Ala Glu Pro Ala 90 95 100 acg ctc ctg gcc gac acg ccg gtt aac gac ggc gcc tgg cac agc gtg 450 Thr Leu Leu Ala Asp Thr Pro Val Asn Asp Gly Ala Trp His Ser Val 105 110 115 cgc atc cgc cgc cag ttc cgc aac acc acg ctc ttc atc gac cag gtg 498 Arg Ile Arg Arg Gln Phe Arg Asn Thr Thr Leu Phe Ile Asp Gln Val 120 125 130 gag gcc aag tgg gtg gag gtc aag tcc aag cgc agg gac atg acg gtg 546 Glu Ala Lys Trp Val Glu Val Lys Ser Lys Arg Arg Asp Met Thr Val 135 140 145 ttc agc ggc ctt ttc gtc ggg ggg ctg ccc ccg gaa ctg cgc gcc gcg 594 Phe Ser Gly Leu Phe Val Gly Gly Leu Pro Pro Glu Leu Arg Ala Ala 150 155 160 165 gcg ctc aag ctc acc ctg gcc tcg gtg agg gag cgg gag ccc ttc aag 642 Ala Leu Lys Leu Thr Leu Ala Ser Val Arg Glu Arg Glu Pro Phe Lys 170 175 180 ggg tgg att cgt gac gtg agg gtc aac tcc tcg cag gtc ctg ccc gtg 690 Gly Trp Ile Arg Asp Val Arg Val Asn Ser Ser Gln Val Leu Pro Val 185 190 195 gac agc ggc gag gtg aag ctg gac gat gag ccg ccc aac agc ggc ggg 738 Asp Ser Gly Glu Val Lys Leu Asp Asp Glu Pro Pro Asn Ser Gly Gly 200 205 210 gga agc ccg tgc gag gcg ggc gag gag ggc gag ggc ggg gtg tgc ctc 786 Gly Ser Pro Cys Glu Ala Gly Glu Glu Gly Glu Gly Gly Val Cys Leu 215 220 225 aac gga ggt gtg tgc tcc gtg gtg gac gac cag gcc gtg tgc gac tgc 834 Asn Gly Gly Val Cys Ser Val Val Asp Asp Gln Ala Val Cys Asp Cys 230 235 240 245 tcg cga acc ggc ttc cgc ggc aag gac tgc agc caa gaa gac aac aat 882 Ser Arg Thr Gly Phe Arg Gly Lys Asp Cys Ser Gln Glu Asp Asn Asn 250 255 260 gtg gaa ggt ctg gcg cac ctg atg atg ggc gac caa ggt aaa agt aaa 930 Val Glu Gly Leu Ala His Leu Met Met Gly Asp Gln Gly Lys Ser Lys 265 270 275 gga aaa gaa gaa tat att gcc acg ttc aaa gga tct gaa tac ttc tgc 978 Gly Lys Glu Glu Tyr Ile Ala Thr Phe Lys Gly Ser Glu Tyr Phe Cys 280 285 290 tac gac ttg tct caa aac ccc att caa agc agc agt gat gaa ata act 1026 Tyr Asp Leu Ser Gln Asn Pro Ile Gln Ser Ser Ser Asp Glu Ile Thr 295 300 305 ctg tca ttt aaa acc ctt cag agg aat gga ctg atg ctt cac act ggg 1074 Leu Ser Phe Lys Thr Leu Gln Arg Asn Gly Leu Met Leu His Thr Gly 310 315 320 325 aaa tcg gct gat tat gtc aat ctt gcc ctg aaa aat gga gct gtc tct 1122 Lys Ser Ala Asp Tyr Val Asn Leu Ala Leu Lys Asn Gly Ala Val Ser 330 335 340 ctg gtc att aat ttg gga tca ggg gcc ttt gaa gca cta gtg gag cct 1170 Leu Val Ile Asn Leu Gly Ser Gly Ala Phe Glu Ala Leu Val Glu Pro 345 350 355 gtg aat gga aag ttt aat gat aat gcc tgg cat gat gtg aaa gtc acc 1218 Val Asn Gly Lys Phe Asn Asp Asn Ala Trp His Asp Val Lys Val Thr 360 365 370 agg aat ctg cgt cag cac tca ggc att gga cac gct atg gta aac aaa 1266 Arg Asn Leu Arg Gln His Ser Gly Ile Gly His Ala Met Val Asn Lys 375 380 385 cta cat tgt tcg gtg aca ata tca gtg gat ggg att ctt acc aca acg 1314 Leu His Cys Ser Val Thr Ile Ser Val Asp Gly Ile Leu Thr Thr Thr 390 395 400 405 ggc tac acg caa gaa gat tat acc atg ctg ggg tct gat gac ttt ttc 1362 Gly Tyr Thr Gln Glu Asp Tyr Thr Met Leu Gly Ser Asp Asp Phe Phe 410 415 420 tat gtt gga ggc agt ccc agc aca gcc gac ctt cca ggg tca cca gtc 1410 Tyr Val Gly Gly Ser Pro Ser Thr Ala Asp Leu Pro Gly Ser Pro Val 425 430 435 agt aac aac ttt atg ggc tgt ctc aaa gag gtt gta tat aaa aat aat 1458 Ser Asn Asn Phe Met Gly Cys Leu Lys Glu Val Val Tyr Lys Asn Asn 440 445 450 gat gtg agg ctg gaa tta tct cga ctt gcc aag caa gga gat cct aag 1506 Asp Val Arg Leu Glu Leu Ser Arg Leu Ala Lys Gln Gly Asp Pro Lys 455 460 465 atg aag atc cat gga gtg gtg gca ttt aaa tgt gag aat gtt gca act 1554 Met Lys Ile His Gly Val Val Ala Phe Lys Cys Glu Asn Val Ala Thr 470 475 480 485 tta gac cca atc acc ttt gaa acc cca gag tct ttc atc tct ttg cct 1602 Leu Asp Pro Ile Thr Phe Glu Thr Pro Glu Ser Phe Ile Ser Leu Pro 490 495 500 aaa tgg aat gca aag aaa act ggc tcc ata tca ttt gat ttc cgt aca 1650 Lys Trp Asn Ala Lys Lys Thr Gly Ser Ile Ser Phe Asp Phe Arg Thr 505 510 515 aca gag cca aat ggc ctc atc tta ttt agc cat ggc aag cca aga cat 1698 Thr Glu Pro Asn Gly Leu Ile Leu Phe Ser His Gly Lys Pro Arg His 520 525 530 cag aaa gat gcc aag cac cca cag atg ata aag gtg gac ttc ttt gct 1746 Gln Lys Asp Ala Lys His Pro Gln Met Ile Lys Val Asp Phe Phe Ala 535 540 545 att gag atg cta gat ggc cac ctc tac ctc ctc ctg gac atg ggg tca 1794 Ile Glu Met Leu Asp Gly His Leu Tyr Leu Leu Leu Asp Met Gly Ser 550 555 560 565 ggt act ata aaa ata aaa gcc ctg ttg aag aaa gtg aat gat gga gaa 1842 Gly Thr Ile Lys Ile Lys Ala Leu Leu Lys Lys Val Asn Asp Gly Glu 570 575 580 tgg tat cat gtg gac ttc cag aga gac gga cgg tca ggt acc att tct 1890 Trp Tyr His Val Asp Phe Gln Arg Asp Gly Arg Ser Gly Thr Ile Ser 585 590 595 gtc aac acg ttg cgt act ccc tac act gct cct ggt gag agt gag att 1938 Val Asn Thr Leu Arg Thr Pro Tyr Thr Ala Pro Gly Glu Ser Glu Ile 600 605 610 ctg gac ctg gat gat gag ttg tac ctg ggg ggg ctg cca gaa aat aaa 1986 Leu Asp Leu Asp Asp Glu Leu Tyr Leu Gly Gly Leu Pro Glu Asn Lys 615 620 625 gct ggc ctt gtc ttc ccc acc gag gtg tgg act gct ctg ctc aac tat 2034 Ala Gly Leu Val Phe Pro Thr Glu Val Trp Thr Ala Leu Leu Asn Tyr 630 635 640 645 ggc tac gtg ggc tgc atc agg gat ttg ttc atc gat ggc caa agc aaa 2082 Gly Tyr Val Gly Cys Ile Arg Asp Leu Phe Ile Asp Gly Gln Ser Lys 650 655 660 gat atc cgg caa atg gct gaa gtt caa agt act gct gga gtg aag cct 2130 Asp Ile Arg Gln Met Ala Glu Val Gln Ser Thr Ala Gly Val Lys Pro 665 670 675 tcc tgc tca aag gaa aca gca aaa ccg tgc ctt agc aac cct tgc aaa 2178 Ser Cys Ser Lys Glu Thr Ala Lys Pro Cys Leu Ser Asn Pro Cys Lys 680 685 690 aac aat ggc atg tgc agg gat ggg tgg aac aga tat gtc tgt gat tgt 2226 Asn Asn Gly Met Cys Arg Asp Gly Trp Asn Arg Tyr Val Cys Asp Cys 695 700 705 tcc gga aca ggc tat ctt ggc agg tcc tgt gag aga gag gca acg gtt 2274 Ser Gly Thr Gly Tyr Leu Gly Arg Ser Cys Glu Arg Glu Ala Thr Val 710 715 720 725 ttg agc tat gat ggg agc atg ttt atg aaa att cag ctc ccc gta gtc 2322 Leu Ser Tyr Asp Gly Ser Met Phe Met Lys Ile Gln Leu Pro Val Val 730 735 740 atg cat acg gag gct gag gat gtt tcc tta cgg ttc cga tcc cag cgt 2370 Met His Thr Glu Ala Glu Asp Val Ser Leu Arg Phe Arg Ser Gln Arg 745 750 755 gca tat ggc att ctg atg gca acc act tct aga gac tct gct gac acc 2418 Ala Tyr Gly Ile Leu Met Ala Thr Thr Ser Arg Asp Ser Ala Asp Thr 760 765 770 ctc cgc ctg gag cta gac gca gga cgt gtg aaa ctg acg gtc aat cta 2466 Leu Arg Leu Glu Leu Asp Ala Gly Arg Val Lys Leu Thr Val Asn Leu 775 780 785 gat tgt atc agg att aac tgt aat tcc agc aaa ggt ccc gag act ctt 2514 Asp Cys Ile Arg Ile Asn Cys Asn Ser Ser Lys Gly Pro Glu Thr Leu 790 795 800 805 ttt gct ggc tat aac ctc aat gat aac gag tgg cac aca gtg cgt gta 2562 Phe Ala Gly Tyr Asn Leu Asn Asp Asn Glu Trp His Thr Val Arg Val 810 815 820 gtt cgg cgt gga aaa agt tta aag tta aca gtg gat gac caa cag gcc 2610 Val Arg Arg Gly Lys Ser Leu Lys Leu Thr Val Asp Asp Gln Gln Ala 825 830 835 atg aca ggt caa atg gca ggt gat cat act agg ctg gag ttc cat aac 2658 Met Thr Gly Gln Met Ala Gly Asp His Thr Arg Leu Glu Phe His Asn 840 845 850 ata gag act ggc atc atc aca gaa cga cgg tat ctt tct tct gtc ccc 2706 Ile Glu Thr Gly Ile Ile Thr Glu Arg Arg Tyr Leu Ser Ser Val Pro 855 860 865 tcc aac ttc att gga cac ctg cag agc ttg aca ttt aat gga atg gca 2754 Ser Asn Phe Ile Gly His Leu Gln Ser Leu Thr Phe Asn Gly Met Ala 870 875 880 885 tac att gac ctg tgt aaa aat ggc gac ata gat tac tgt gag ctt aat 2802 Tyr Ile Asp Leu Cys Lys Asn Gly Asp Ile Asp Tyr Cys Glu Leu Asn 890 895 900 gcc aga ttt ggc ttc agg aac atc ata gca gat cct gtc acc ttc aag 2850 Ala Arg Phe Gly Phe Arg Asn Ile Ile Ala Asp Pro Val Thr Phe Lys 905 910 915 acc aaa tcg agc tat gtt gcc tta gct acc ttg caa gcc tac act tct 2898 Thr Lys Ser Ser Tyr Val Ala Leu Ala Thr Leu Gln Ala Tyr Thr Ser 920 925 930 atg cat ctt ttt ttc cag ttc aag aca aca tcc cta gat gga tta att 2946 Met His Leu Phe Phe Gln Phe Lys Thr Thr Ser Leu Asp Gly Leu Ile 935 940 945 cta tat aac agt ggg gat gga aat gac ttt att gtg gtt gaa tta gtt 2994 Leu Tyr Asn Ser Gly Asp Gly Asn Asp Phe Ile Val Val Glu Leu Val 950 955 960 965 aaa ggg tac tta cat tac gtg ttt gat ttg gga aat ggt gct aac ctc 3042 Lys Gly Tyr Leu His Tyr Val Phe Asp Leu Gly Asn Gly Ala Asn Leu 970 975 980 atc aaa gga agc tca aat aaa cct ctc aat gac aat cag tgg cac aac 3090 Ile Lys Gly Ser Ser Asn Lys Pro Leu Asn Asp Asn Gln Trp His Asn 985 990 995 gtg atg ata tca agg gac acc agc aac ctc cac act gta aag att gac 3138 Val Met Ile Ser Arg Asp Thr Ser Asn Leu His Thr Val Lys Ile Asp 1000 1005 1010 aca aaa atc aca acg caa atc acc gcc gga gcc agg aac tta gac ctc 3186 Thr Lys Ile Thr Thr Gln Ile Thr Ala Gly Ala Arg Asn Leu Asp Leu 1015 1020 1025 aag agt gac tta tat ata gga gga gta gct aaa gaa aca tac aaa tcc 3234 Lys Ser Asp Leu Tyr Ile Gly Gly Val Ala Lys Glu Thr Tyr Lys Ser 1030 1035 1040 1045 tta cca aaa ctt gta cat gcc aaa gaa ggc ttt caa ggc tgc ctg gca 3282 Leu Pro Lys Leu Val His Ala Lys Glu Gly Phe Gln Gly Cys Leu Ala 1050 1055 1060 tca gtt gat tta aat gga cgg ctt ccg gac ctc atc tcc gat gct ctt 3330 Ser Val Asp Leu Asn Gly Arg Leu Pro Asp Leu Ile Ser Asp Ala Leu 1065 1070 1075 ttc tgc aac gga cag atc gag aga gga tgt gaa ggg ccc agc aca acc 3378 Phe Cys Asn Gly Gln Ile Glu Arg Gly Cys Glu Gly Pro Ser Thr Thr 1080 1085 1090 tgc caa gag gac tca tgt tcc aat caa ggt gtg tgc ttg caa caa tgg 3426 Cys Gln Glu Asp Ser Cys Ser Asn Gln Gly Val Cys Leu Gln Gln Trp 1095 1100 1105 gat ggc ttc agc tgt gac tgt agt atg act tcc ttc agt gga cca ctc 3474 Asp Gly Phe Ser Cys Asp Cys Ser Met Thr Ser Phe Ser Gly Pro Leu 1110 1115 1120 1125 tgc aat gac cct ggg acg aca tat atc ttt agc aaa ggt ggt gga caa 3522 Cys Asn Asp Pro Gly Thr Thr Tyr Ile Phe Ser Lys Gly Gly Gly Gln 1130 1135 1140 atc acg tat aag tgg cct cct aat gac cga ccc agt aca cga gca gac 3570 Ile Thr Tyr Lys Trp Pro Pro Asn Asp Arg Pro Ser Thr Arg Ala Asp 1145 1150 1155 aga ctg gcc ata ggt ttt agc act gtt cag aaa gaa gcc gta ttg gtg 3618 Arg Leu Ala Ile Gly Phe Ser Thr Val Gln Lys Glu Ala Val Leu Val 1160 1165 1170 cga gtg gac agt tct tca ggc ttg ggt gac tac cta gaa ctg cat ata 3666 Arg Val Asp Ser Ser Ser Gly Leu Gly Asp Tyr Leu Glu Leu His Ile 1175 1180 1185 cac cag gga aaa att gga gtt aag ttt aat gtt ggg aca gat gac atc 3714 His Gln Gly Lys Ile Gly Val Lys Phe Asn Val Gly Thr Asp Asp Ile 1190 1195 1200 1205 gcc att gaa gaa tcc aat gca atc att aat gat ggg aaa tac cat gta 3762 Ala Ile Glu Glu Ser Asn Ala Ile Ile Asn Asp Gly Lys Tyr His Val 1210 1215 1220 gtt cgt ttc acg agg agt ggt ggc aat gcc acg ttg cag gtg gac agc 3810 Val Arg Phe Thr Arg Ser Gly Gly Asn Ala Thr Leu Gln Val Asp Ser 1225 1230 1235 tgg cca gtg atc gag cgc tac cct gca gga aac aat gat aac gag cgc 3858 Trp Pro Val Ile Glu Arg Tyr Pro Ala Gly Asn Asn Asp Asn Glu Arg 1240 1245 1250 ctg gcg att gct aga cag cga att cca tat cga ctt ggt cga gta gtt 3906 Leu Ala Ile Ala Arg Gln Arg Ile Pro Tyr Arg Leu Gly Arg Val Val 1255 1260 1265 gat gaa tgg cta ctc gac aaa ggg cgt cag ctc aca atc ttc aat agc 3954 Asp Glu Trp Leu Leu Asp Lys Gly Arg Gln Leu Thr Ile Phe Asn Ser 1270 1275 1280 1285 caa gca acc ata ata att ggc ggg aaa gag cag ggc cag ccc ttc cag 4002 Gln Ala Thr Ile Ile Ile Gly Gly Lys Glu Gln Gly Gln Pro Phe Gln 1290 1295 1300 ggc cag ctc tct ggg ctg tac tac aat ggc ttg aaa gtt ctg aat atg 4050 Gly Gln Leu Ser Gly Leu Tyr Tyr Asn Gly Leu Lys Val Leu Asn Met 1305 1310 1315 gca gcc gaa aac gat gcc aac atc gcc ata gtg gga aat gtg aga ctg 4098 Ala Ala Glu Asn Asp Ala Asn Ile Ala Ile Val Gly Asn Val Arg Leu 1320 1325 1330 gtt ggt gaa gtg cct tcc tct atg aca act gag tca aca gcc act gcc 4146 Val Gly Glu Val Pro Ser Ser Met Thr Thr Glu Ser Thr Ala Thr Ala 1335 1340 1345 atg caa tca gag atg tcc aca tca att atg gag act acc acg acc ctg 4194 Met Gln Ser Glu Met Ser Thr Ser Ile Met Glu Thr Thr Thr Thr Leu 1350 1355 1360 1365 gct act agc aca gcc aga aga gga aag ccc ccg aca aaa gaa ccc att 4242 Ala Thr Ser Thr Ala Arg Arg Gly Lys Pro Pro Thr Lys Glu Pro Ile 1370 1375 1380 agc cag acc aca gat gac atc ctt gtg gcc tca gca gag tgt ccc agc 4290 Ser Gln Thr Thr Asp Asp Ile Leu Val Ala Ser Ala Glu Cys Pro Ser 1385 1390 1395 gat gat gag gac att gac ccc tgt gag ccg agc tca ggt ggg tta gcc 4338 Asp Asp Glu Asp Ile Asp Pro Cys Glu Pro Ser Ser Gly Gly Leu Ala 1400 1405 1410 aac cca acc cga gca ggc ggc aga gag ccg tat cca ggc tca gca gaa 4386 Asn Pro Thr Arg Ala Gly Gly Arg Glu Pro Tyr Pro Gly Ser Ala Glu 1415 1420 1425 gtg atc cgg gag tcc agc agc acc acg ggt atg gtc gtt ggg ata gta 4434 Val Ile Arg Glu Ser Ser Ser Thr Thr Gly Met Val Val Gly Ile Val 1430 1435 1440 1445 gcc gct gcc gcc ctg tgc atc ctt atc ctc ctc tat gcc atg tac aag 4482 Ala Ala Ala Ala Leu Cys Ile Leu Ile Leu Leu Tyr Ala Met Tyr Lys 1450 1455 1460 tac aga aac cgg gat gaa ggc tca tac cat gtg gac gag agt cga aac 4530 Tyr Arg Asn Arg Asp Glu Gly Ser Tyr His Val Asp Glu Ser Arg Asn 1465 1470 1475 tac atc agt aac tca gca cag tcc aat ggg gct gtt gta aag gag aaa 4578 Tyr Ile Ser Asn Ser Ala Gln Ser Asn Gly Ala Val Val Lys Glu Lys 1480 1485 1490 caa ccc agc agt gcg aaa agc tcc aac aaa aat aag aaa aac aag gat 4626 Gln Pro Ser Ser Ala Lys Ser Ser Asn Lys Asn Lys Lys Asn Lys Asp 1495 1500 1505 aaa gag tat tat gtc tgatcccaag atcttaaatg gacacttgta tagaaatagt 4681 Lys Glu Tyr Tyr Val 1510 cttcatttta tctgagacat aatataaact tatttacttt cctttttatg aagcacatac 4741 aaaagaagac agagaatgca atcaggaagg aaagactttt taaaaaataa aaacaagtat 4801 ctcatgctct tgtttctcaa aaaagaaaaa caaaaaacaa aaaacagggg ccaataaatt 4861 ccctaacatc cacagtgttt tcatttactc tgcttgtctt tatgttgctg gaacatttct 4921 aaaagacagt gatgaccgca cgcattcata aagcaaagga gtactacagc atcaaggcac 4981 aacacaaaaa ccaacacaaa acataacaca aaaaagaagc tacctatgat cctggattta 5041 gccaaagtgc tagcgctttc ctgagaagtc agtccaattg ccagagaaga ctgtcctttt 5101 gagtgactca acctgcaaac ctttaagagt ttgccgcctg gtgcaactgg agcagtggtt 5161 ggaacttgca tttgaaacaa agtgctggct tttttgaaga cttgtgtagg aacacattca 5221 aaaagcccct ttctggttgt gagagaggaa aaaaaaagta tggaggcctt attttcaaaa 5281 atgtgaaata taaggcacgt tttcacacaa aatttcaaaa caaaaacaag agggcataga 5341 tgcaatcatt gggaaatttt catgcacgct tattatgtta ttacatatgt ttatataaaa 5401 tccatctctg tgtgctttct ggactgtgat aagtgacgtt ttatagcctg ttgtatagaa 5461 aatgcaaaat atatctctgc tcttcagcca tttttggtaa attcaatgtt ataagtgttg 5521 ctaagtatag ggagttttat gacatcagag caacaattat ttcagttggg tttttctttt 5581 ttttgccacc attataaatt gccacaatta cttactttta ttttttaaag aaattacagt 5641 gtagtgttta ttctaaggaa gatatgtatg aatgtatata caaagactca gctacttctt 5701 ttcttatatg tacagccttc attctgttgc aattaagttt tagtacttgt atgaaaggtg 5761 tgaattagaa agtcacatat atacatatgt atcttataat cttttctccc tgaaatactc 5821 acattcccac atacattcac tattttcaca cacacacaca cacacacaca cacacacaca 5881 cacacacacg aatccacagc aatccatcag atatgctgga agatccaaac gtgcatacag 5941 tagcaaatat ttattgacaa attgaaaagc aggaaggaag agggttgtgc caaggtattg 6001 atgacaaatg gggtgatttg cttcattgag atcttgctcc caggtaacct taagaagatt 6061 ttagtcccta aagaaatgaa cctttcctta tcaaatagaa tatcactgat atactgctgc 6121 atgaataaga accattatgt gggcaggtta tggaagcaaa attggttaat ctacacctta 6181 actctggctg ctgcaattga aaactttctt tctaataaaa taatatatat atctctgaa 6240 36 1514 PRT Homo sapiens 36 Met Gly Thr Ala Leu Leu Gln Arg Gly Gly Cys Phe Leu Leu Cys Leu 1 5 10 15 Ser Leu Leu Leu Leu Gly Cys Trp Ala Glu Leu Gly Ser Gly Leu Glu 20 25 30 Phe Pro Gly Ala Glu Gly Gln Trp Thr Arg Phe Pro Lys Trp Asn Ala 35 40 45 Cys Cys Glu Ser Glu Met Ser Phe Gln Leu Lys Thr Arg Ser Ala Arg 50 55 60 Gly Leu Val Leu Tyr Phe Asp Asp Glu Gly Phe Cys Asp Phe Leu Glu 65 70 75 80 Leu Ile Leu Thr Arg Gly Gly Arg Leu Gln Leu Ser Phe Ser Ile Phe 85 90 95 Cys Ala Glu Pro Ala Thr Leu Leu Ala Asp Thr Pro Val Asn Asp Gly 100 105 110 Ala Trp His Ser Val Arg Ile Arg Arg Gln Phe Arg Asn Thr Thr Leu 115 120 125 Phe Ile Asp Gln Val Glu Ala Lys Trp Val Glu Val Lys Ser Lys Arg 130 135 140 Arg Asp Met Thr Val Phe Ser Gly Leu Phe Val Gly Gly Leu Pro Pro 145 150 155 160 Glu Leu Arg Ala Ala Ala Leu Lys Leu Thr Leu Ala Ser Val Arg Glu 165 170 175 Arg Glu Pro Phe Lys Gly Trp Ile Arg Asp Val Arg Val Asn Ser Ser 180 185 190 Gln Val Leu Pro Val Asp Ser Gly Glu Val Lys Leu Asp Asp Glu Pro 195 200 205 Pro Asn Ser Gly Gly Gly Ser Pro Cys Glu Ala Gly Glu Glu Gly Glu 210 215 220 Gly Gly Val Cys Leu Asn Gly Gly Val Cys Ser Val Val Asp Asp Gln 225 230 235 240 Ala Val Cys Asp Cys Ser Arg Thr Gly Phe Arg Gly Lys Asp Cys Ser 245 250 255 Gln Glu Asp Asn Asn Val Glu Gly Leu Ala His Leu Met Met Gly Asp 260 265 270 Gln Gly Lys Ser Lys Gly Lys Glu Glu Tyr Ile Ala Thr Phe Lys Gly 275 280 285 Ser Glu Tyr Phe Cys Tyr Asp Leu Ser Gln Asn Pro Ile Gln Ser Ser 290 295 300 Ser Asp Glu Ile Thr Leu Ser Phe Lys Thr Leu Gln Arg Asn Gly Leu 305 310 315 320 Met Leu His Thr Gly Lys Ser Ala Asp Tyr Val Asn Leu Ala Leu Lys 325 330 335 Asn Gly Ala Val Ser Leu Val Ile Asn Leu Gly Ser Gly Ala Phe Glu 340 345 350 Ala Leu Val Glu Pro Val Asn Gly Lys Phe Asn Asp Asn Ala Trp His 355 360 365 Asp Val Lys Val Thr Arg Asn Leu Arg Gln His Ser Gly Ile Gly His 370 375 380 Ala Met Val Asn Lys Leu His Cys Ser Val Thr Ile Ser Val Asp Gly 385 390 395 400 Ile Leu Thr Thr Thr Gly Tyr Thr Gln Glu Asp Tyr Thr Met Leu Gly 405 410 415 Ser Asp Asp Phe Phe Tyr Val Gly Gly Ser Pro Ser Thr Ala Asp Leu 420 425 430 Pro Gly Ser Pro Val Ser Asn Asn Phe Met Gly Cys Leu Lys Glu Val 435 440 445 Val Tyr Lys Asn Asn Asp Val Arg Leu Glu Leu Ser Arg Leu Ala Lys 450 455 460 Gln Gly Asp Pro Lys Met Lys Ile His Gly Val Val Ala Phe Lys Cys 465 470 475 480 Glu Asn Val Ala Thr Leu Asp Pro Ile Thr Phe Glu Thr Pro Glu Ser 485 490 495 Phe Ile Ser Leu Pro Lys Trp Asn Ala Lys Lys Thr Gly Ser Ile Ser 500 505 510 Phe Asp Phe Arg Thr Thr Glu Pro Asn Gly Leu Ile Leu Phe Ser His 515 520 525 Gly Lys Pro Arg His Gln Lys Asp Ala Lys His Pro Gln Met Ile Lys 530 535 540 Val Asp Phe Phe Ala Ile Glu Met Leu Asp Gly His Leu Tyr Leu Leu 545 550 555 560 Leu Asp Met Gly Ser Gly Thr Ile Lys Ile Lys Ala Leu Leu Lys Lys 565 570 575 Val Asn Asp Gly Glu Trp Tyr His Val Asp Phe Gln Arg Asp Gly Arg 580 585 590 Ser Gly Thr Ile Ser Val Asn Thr Leu Arg Thr Pro Tyr Thr Ala Pro 595 600 605 Gly Glu Ser Glu Ile Leu Asp Leu Asp Asp Glu Leu Tyr Leu Gly Gly 610 615 620 Leu Pro Glu Asn Lys Ala Gly Leu Val Phe Pro Thr Glu Val Trp Thr 625 630 635 640 Ala Leu Leu Asn Tyr Gly Tyr Val Gly Cys Ile Arg Asp Leu Phe Ile 645 650 655 Asp Gly Gln Ser Lys Asp Ile Arg Gln Met Ala Glu Val Gln Ser Thr 660 665 670 Ala Gly Val Lys Pro Ser Cys Ser Lys Glu Thr Ala Lys Pro Cys Leu 675 680 685 Ser Asn Pro Cys Lys Asn Asn Gly Met Cys Arg Asp Gly Trp Asn Arg 690 695 700 Tyr Val Cys Asp Cys Ser Gly Thr Gly Tyr Leu Gly Arg Ser Cys Glu 705 710 715 720 Arg Glu Ala Thr Val Leu Ser Tyr Asp Gly Ser Met Phe Met Lys Ile 725 730 735 Gln Leu Pro Val Val Met His Thr Glu Ala Glu Asp Val Ser Leu Arg 740 745 750 Phe Arg Ser Gln Arg Ala Tyr Gly Ile Leu Met Ala Thr Thr Ser Arg 755 760 765 Asp Ser Ala Asp Thr Leu Arg Leu Glu Leu Asp Ala Gly Arg Val Lys 770 775 780 Leu Thr Val Asn Leu Asp Cys Ile Arg Ile Asn Cys Asn Ser Ser Lys 785 790 795 800 Gly Pro Glu Thr Leu Phe Ala Gly Tyr Asn Leu Asn Asp Asn Glu Trp 805 810 815 His Thr Val Arg Val Val Arg Arg Gly Lys Ser Leu Lys Leu Thr Val 820 825 830 Asp Asp Gln Gln Ala Met Thr Gly Gln Met Ala Gly Asp His Thr Arg 835 840 845 Leu Glu Phe His Asn Ile Glu Thr Gly Ile Ile Thr Glu Arg Arg Tyr 850 855 860 Leu Ser Ser Val Pro Ser Asn Phe Ile Gly His Leu Gln Ser Leu Thr 865 870 875 880 Phe Asn Gly Met Ala Tyr Ile Asp Leu Cys Lys Asn Gly Asp Ile Asp 885 890 895 Tyr Cys Glu Leu Asn Ala Arg Phe Gly Phe Arg Asn Ile Ile Ala Asp 900 905 910 Pro Val Thr Phe Lys Thr Lys Ser Ser Tyr Val Ala Leu Ala Thr Leu 915 920 925 Gln Ala Tyr Thr Ser Met His Leu Phe Phe Gln Phe Lys Thr Thr Ser 930 935 940 Leu Asp Gly Leu Ile Leu Tyr Asn Ser Gly Asp Gly Asn Asp Phe Ile 945 950 955 960 Val Val Glu Leu Val Lys Gly Tyr Leu His Tyr Val Phe Asp Leu Gly 965 970 975 Asn Gly Ala Asn Leu Ile Lys Gly Ser Ser Asn Lys Pro Leu Asn Asp 980 985 990 Asn Gln Trp His Asn Val Met Ile Ser Arg Asp Thr Ser Asn Leu His 995 1000 1005 Thr Val Lys Ile Asp Thr Lys Ile Thr Thr Gln Ile Thr Ala Gly Ala 1010 1015 1020 Arg Asn Leu Asp Leu Lys Ser Asp Leu Tyr Ile Gly Gly Val Ala Lys 1025 1030 1035 1040 Glu Thr Tyr Lys Ser Leu Pro Lys Leu Val His Ala Lys Glu Gly Phe 1045 1050 1055 Gln Gly Cys Leu Ala Ser Val Asp Leu Asn Gly Arg Leu Pro Asp Leu 1060 1065 1070 Ile Ser Asp Ala Leu Phe Cys Asn Gly Gln Ile Glu Arg Gly Cys Glu 1075 1080 1085 Gly Pro Ser Thr Thr Cys Gln Glu Asp Ser Cys Ser Asn Gln Gly Val 1090 1095 1100 Cys Leu Gln Gln Trp Asp Gly Phe Ser Cys Asp Cys Ser Met Thr Ser 1105 1110 1115 1120 Phe Ser Gly Pro Leu Cys Asn Asp Pro Gly Thr Thr Tyr Ile Phe Ser 1125 1130 1135 Lys Gly Gly Gly Gln Ile Thr Tyr Lys Trp Pro Pro Asn Asp Arg Pro 1140 1145 1150 Ser Thr Arg Ala Asp Arg Leu Ala Ile Gly Phe Ser Thr Val Gln Lys 1155 1160 1165 Glu Ala Val Leu Val Arg Val Asp Ser Ser Ser Gly Leu Gly Asp Tyr 1170 1175 1180 Leu Glu Leu His Ile His Gln Gly Lys Ile Gly Val Lys Phe Asn Val 1185 1190 1195 1200 Gly Thr Asp Asp Ile Ala Ile Glu Glu Ser Asn Ala Ile Ile Asn Asp 1205 1210 1215 Gly Lys Tyr His Val Val Arg Phe Thr Arg Ser Gly Gly Asn Ala Thr 1220 1225 1230 Leu Gln Val Asp Ser Trp Pro Val Ile Glu Arg Tyr Pro Ala Gly Asn 1235 1240 1245 Asn Asp Asn Glu Arg Leu Ala Ile Ala Arg Gln Arg Ile Pro Tyr Arg 1250 1255 1260 Leu Gly Arg Val Val Asp Glu Trp Leu Leu Asp Lys Gly Arg Gln Leu 1265 1270 1275 1280 Thr Ile Phe Asn Ser Gln Ala Thr Ile Ile Ile Gly Gly Lys Glu Gln 1285 1290 1295 Gly Gln Pro Phe Gln Gly Gln Leu Ser Gly Leu Tyr Tyr Asn Gly Leu 1300 1305 1310 Lys Val Leu Asn Met Ala Ala Glu Asn Asp Ala Asn Ile Ala Ile Val 1315 1320 1325 Gly Asn Val Arg Leu Val Gly Glu Val Pro Ser Ser Met Thr Thr Glu 1330 1335 1340 Ser Thr Ala Thr Ala Met Gln Ser Glu Met Ser Thr Ser Ile Met Glu 1345 1350 1355 1360 Thr Thr Thr Thr Leu Ala Thr Ser Thr Ala Arg Arg Gly Lys Pro Pro 1365 1370 1375 Thr Lys Glu Pro Ile Ser Gln Thr Thr Asp Asp Ile Leu Val Ala Ser 1380 1385 1390 Ala Glu Cys Pro Ser Asp Asp Glu Asp Ile Asp Pro Cys Glu Pro Ser 1395 1400 1405 Ser Gly Gly Leu Ala Asn Pro Thr Arg Ala Gly Gly Arg Glu Pro Tyr 1410 1415 1420 Pro Gly Ser Ala Glu Val Ile Arg Glu Ser Ser Ser Thr Thr Gly Met 1425 1430 1435 1440 Val Val Gly Ile Val Ala Ala Ala Ala Leu Cys Ile Leu Ile Leu Leu 1445 1450 1455 Tyr Ala Met Tyr Lys Tyr Arg Asn Arg Asp Glu Gly Ser Tyr His Val 1460 1465 1470 Asp Glu Ser Arg Asn Tyr Ile Ser Asn Ser Ala Gln Ser Asn Gly Ala 1475 1480 1485 Val Val Lys Glu Lys Gln Pro Ser Ser Ala Lys Ser Ser Asn Lys Asn 1490 1495 1500 Lys Lys Asn Lys Asp Lys Glu Tyr Tyr Val 1505 1510 37 1611 DNA Homo sapiens CDS (46)..(1461) 37 aaactttgcc tcccgcggcg gctgcccctc ggcgggcgcc ccgcc atg tac cag agg 57 Met Tyr Gln Arg 1 atg ctc cgg tgc ggc gcc gag ctg ggc tcg ccc ggg ggc ggc ggc ggc 105 Met Leu Arg Cys Gly Ala Glu Leu Gly Ser Pro Gly Gly Gly Gly Gly 5 10 15 20 ggc ggc ggc ggc ggc ggc gca ggg ggg cgc ctg gcc ctg ctt tgg ata 153 Gly Gly Gly Gly Gly Gly Ala Gly Gly Arg Leu Ala Leu Leu Trp Ile 25 30 35 gtc ccg ctc acc ctc agc ggc ctc cta gga gtg gcg tgg ggg gca tcc 201 Val Pro Leu Thr Leu Ser Gly Leu Leu Gly Val Ala Trp Gly Ala Ser 40 45 50 agt ttg gga gcg cac cac atc cac cat ttc cat ggc agc agc aag cat 249 Ser Leu Gly Ala His His Ile His His Phe His Gly Ser Ser Lys His 55 60 65 cat tca gtg cct att gca atc tac agg tca ccg gca tcc ttg cga ggc 297 His Ser Val Pro Ile Ala Ile Tyr Arg Ser Pro Ala Ser Leu Arg Gly 70 75 80 gga cac gct ggg acg aca tat atc ttt agc aaa ggt ggt gga caa atc 345 Gly His Ala Gly Thr Thr Tyr Ile Phe Ser Lys Gly Gly Gly Gln Ile 85 90 95 100 acg tat aag tgg cct cct aat gac cga ccc agt aca cga gca gac aga 393 Thr Tyr Lys Trp Pro Pro Asn Asp Arg Pro Ser Thr Arg Ala Asp Arg 105 110 115 ctg gcc ata ggt ttt agc act gtt cag aaa gaa gcc gta ttg gtg cga 441 Leu Ala Ile Gly Phe Ser Thr Val Gln Lys Glu Ala Val Leu Val Arg 120 125 130 gtg gac agt tct tca ggc ttg ggt gac tac cta gaa ctg cat ata cac 489 Val Asp Ser Ser Ser Gly Leu Gly Asp Tyr Leu Glu Leu His Ile His 135 140 145 cag gga aaa att gga gtt aag ttt aat gtt ggg aca gat gac atc gcc 537 Gln Gly Lys Ile Gly Val Lys Phe Asn Val Gly Thr Asp Asp Ile Ala 150 155 160 att gaa gaa tcc aat gca atc att aat gat ggg aaa tac cat gta gtt 585 Ile Glu Glu Ser Asn Ala Ile Ile Asn Asp Gly Lys Tyr His Val Val 165 170 175 180 cgt ttc acg agg agt ggt ggc aat gcc acg ttg cag gtg gac agc tgg 633 Arg Phe Thr Arg Ser Gly Gly Asn Ala Thr Leu Gln Val Asp Ser Trp 185 190 195 cca gtg atc gag cgc tac cct gca gga aac aat gat aac gag cgc ctg 681 Pro Val Ile Glu Arg Tyr Pro Ala Gly Asn Asn Asp Asn Glu Arg Leu 200 205 210 gcg att gct aga cag cga att cca tat cga ctt ggt cga gta gtt gat 729 Ala Ile Ala Arg Gln Arg Ile Pro Tyr Arg Leu Gly Arg Val Val Asp 215 220 225 gaa tgg cta ctc gac aaa ggg cgt cag ctc aca atc ttc aat agc caa 777 Glu Trp Leu Leu Asp Lys Gly Arg Gln Leu Thr Ile Phe Asn Ser Gln 230 235 240 gca acc ata ata att ggc ggg aaa gag cag ggc cag ccc ttc cag ggc 825 Ala Thr Ile Ile Ile Gly Gly Lys Glu Gln Gly Gln Pro Phe Gln Gly 245 250 255 260 cag ctc tct ggg ctg tac tac aat ggc ttg aaa gtt ctg aat atg gca 873 Gln Leu Ser Gly Leu Tyr Tyr Asn Gly Leu Lys Val Leu Asn Met Ala 265 270 275 gcc gaa aac gat gcc aac atc gcc ata gtg gga aat gtg aga ctg gtt 921 Ala Glu Asn Asp Ala Asn Ile Ala Ile Val Gly Asn Val Arg Leu Val 280 285 290 ggt gaa gtg cct tcc tct atg aca act gag tca aca gcc act gcc atg 969 Gly Glu Val Pro Ser Ser Met Thr Thr Glu Ser Thr Ala Thr Ala Met 295 300 305 caa tca gag atg tcc aca tca att atg gag act acc acg acc ctg gct 1017 Gln Ser Glu Met Ser Thr Ser Ile Met Glu Thr Thr Thr Thr Leu Ala 310 315 320 act agc aca gcc aga aga gga aag ccc ccg aca aaa gaa ccc att agc 1065 Thr Ser Thr Ala Arg Arg Gly Lys Pro Pro Thr Lys Glu Pro Ile Ser 325 330 335 340 cag acc aca gat gac atc ctt gtg gcc tca gca gag tgt ccc agc gat 1113 Gln Thr Thr Asp Asp Ile Leu Val Ala Ser Ala Glu Cys Pro Ser Asp 345 350 355 gat gag gac att gac ccc tgt gag ccg agc tca ggt ggg tta gcc aac 1161 Asp Glu Asp Ile Asp Pro Cys Glu Pro Ser Ser Gly Gly Leu Ala Asn 360 365 370 cca acc cga gca ggc ggc aga gag ccg tat cca ggc tca gca gaa gtg 1209 Pro Thr Arg Ala Gly Gly Arg Glu Pro Tyr Pro Gly Ser Ala Glu Val 375 380 385 atc cgg gag tcc agc agc acc acg ggt atg gtc gtt ggg ata gta gcc 1257 Ile Arg Glu Ser Ser Ser Thr Thr Gly Met Val Val Gly Ile Val Ala 390 395 400 gct gcc gcc ctg tgc atc ctt atc ctc ctc tat gcc atg tac aag tac 1305 Ala Ala Ala Leu Cys Ile Leu Ile Leu Leu Tyr Ala Met Tyr Lys Tyr 405 410 415 420 aga aac cgg gat gaa ggc tca tac cat gtg gac gag agt cga aac tac 1353 Arg Asn Arg Asp Glu Gly Ser Tyr His Val Asp Glu Ser Arg Asn Tyr 425 430 435 atc agt aac tca gca cag tcc aat ggg gct gtt gta aag gag aaa caa 1401 Ile Ser Asn Ser Ala Gln Ser Asn Gly Ala Val Val Lys Glu Lys Gln 440 445 450 ccc agc agt gcg aaa agc tcc aac aaa aat aag aaa aac aag gat aaa 1449 Pro Ser Ser Ala Lys Ser Ser Asn Lys Asn Lys Lys Asn Lys Asp Lys 455 460 465 gag tat tat gtc tgatcccaag atcttaaatg gacacttgta tagaaatagt 1501 Glu Tyr Tyr Val 470 cttcatttta tctgagacat aatataaact tatttacttt cctttttatg aagcacatac 1561 aaaagaagac agggaatgca atcaggaagg aaagactttt taaaaaataa 1611 38 472 PRT Homo sapiens 38 Met Tyr Gln Arg Met Leu Arg Cys Gly Ala Glu Leu Gly Ser Pro Gly 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Ala Gly Gly Arg Leu Ala 20 25 30 Leu Leu Trp Ile Val Pro Leu Thr Leu Ser Gly Leu Leu Gly Val Ala 35 40 45 Trp Gly Ala Ser Ser Leu Gly Ala His His Ile His His Phe His Gly 50 55 60 Ser Ser Lys His His Ser Val Pro Ile Ala Ile Tyr Arg Ser Pro Ala 65 70 75 80 Ser Leu Arg Gly Gly His Ala Gly Thr Thr Tyr Ile Phe Ser Lys Gly 85 90 95 Gly Gly Gln Ile Thr Tyr Lys Trp Pro Pro Asn Asp Arg Pro Ser Thr 100 105 110 Arg Ala Asp Arg Leu Ala Ile Gly Phe Ser Thr Val Gln Lys Glu Ala 115 120 125 Val Leu Val Arg Val Asp Ser Ser Ser Gly Leu Gly Asp Tyr Leu Glu 130 135 140 Leu His Ile His Gln Gly Lys Ile Gly Val Lys Phe Asn Val Gly Thr 145 150 155 160 Asp Asp Ile Ala Ile Glu Glu Ser Asn Ala Ile Ile Asn Asp Gly Lys 165 170 175 Tyr His Val Val Arg Phe Thr Arg Ser Gly Gly Asn Ala Thr Leu Gln 180 185 190 Val Asp Ser Trp Pro Val Ile Glu Arg Tyr Pro Ala Gly Asn Asn Asp 195 200 205 Asn Glu Arg Leu Ala Ile Ala Arg Gln Arg Ile Pro Tyr Arg Leu Gly 210 215 220 Arg Val Val Asp Glu Trp Leu Leu Asp Lys Gly Arg Gln Leu Thr Ile 225 230 235 240 Phe Asn Ser Gln Ala Thr Ile Ile Ile Gly Gly Lys Glu Gln Gly Gln 245 250 255 Pro Phe Gln Gly Gln Leu Ser Gly Leu Tyr Tyr Asn Gly Leu Lys Val 260 265 270 Leu Asn Met Ala Ala Glu Asn Asp Ala Asn Ile Ala Ile Val Gly Asn 275 280 285 Val Arg Leu Val Gly Glu Val Pro Ser Ser Met Thr Thr Glu Ser Thr 290 295 300 Ala Thr Ala Met Gln Ser Glu Met Ser Thr Ser Ile Met Glu Thr Thr 305 310 315 320 Thr Thr Leu Ala Thr Ser Thr Ala Arg Arg Gly Lys Pro Pro Thr Lys 325 330 335 Glu Pro Ile Ser Gln Thr Thr Asp Asp Ile Leu Val Ala Ser Ala Glu 340 345 350 Cys Pro Ser Asp Asp Glu Asp Ile Asp Pro Cys Glu Pro Ser Ser Gly 355 360 365 Gly Leu Ala Asn Pro Thr Arg Ala Gly Gly Arg Glu Pro Tyr Pro Gly 370 375 380 Ser Ala Glu Val Ile Arg Glu Ser Ser Ser Thr Thr Gly Met Val Val 385 390 395 400 Gly Ile Val Ala Ala Ala Ala Leu Cys Ile Leu Ile Leu Leu Tyr Ala 405 410 415 Met Tyr Lys Tyr Arg Asn Arg Asp Glu Gly Ser Tyr His Val Asp Glu 420 425 430 Ser Arg Asn Tyr Ile Ser Asn Ser Ala Gln Ser Asn Gly Ala Val Val 435 440 445 Lys Glu Lys Gln Pro Ser Ser Ala Lys Ser Ser Asn Lys Asn Lys Lys 450 455 460 Asn Lys Asp Lys Glu Tyr Tyr Val 465 470 39 1365 DNA Homo sapiens CDS (73)..(1146) 39 acgcgtggag tcctgcgggc cgtggccacc cagcagcgcg gcgccgtgtt cgtggacaag 60 gagaacctca cc atg ccg ggc ctc agg ttc gac aac atc cag gga gat gca 111 Met Pro Gly Leu Arg Phe Asp Asn Ile Gln Gly Asp Ala 1 5 10 gtt aaa gac ttg atg ctt cgc ttt ctg ggt gaa aaa gct gca gca aag 159 Val Lys Asp Leu Met Leu Arg Phe Leu Gly Glu Lys Ala Ala Ala Lys 15 20 25 aga caa gtc cta aat gcc gac tca gtg gaa caa tct ttt gtt gga ttg 207 Arg Gln Val Leu Asn Ala Asp Ser Val Glu Gln Ser Phe Val Gly Leu 30 35 40 45 aaa cag cta atc ctc tgg ttt gtc agg ctg gca cta cta gtg aag ttg 255 Lys Gln Leu Ile Leu Trp Phe Val Arg Leu Ala Leu Leu Val Lys Leu 50 55 60 ggc ctt ttc cag aat gct gag atg gaa ttt gaa ccc ttc gga aat ctt 303 Gly Leu Phe Gln Asn Ala Glu Met Glu Phe Glu Pro Phe Gly Asn Leu 65 70 75 gat cag cca gat ctt tat tac gag tac tac ccg cac gtg tac cct ggg 351 Asp Gln Pro Asp Leu Tyr Tyr Glu Tyr Tyr Pro His Val Tyr Pro Gly 80 85 90 cgc agg ggc tcc atg gtc ccc ttc tcg atg cgc atc ttg cac gcg gag 399 Arg Arg Gly Ser Met Val Pro Phe Ser Met Arg Ile Leu His Ala Glu 95 100 105 ctt cag cag tac ctg ggg aac cca cag gag tcg ctg gat aga ctg cac 447 Leu Gln Gln Tyr Leu Gly Asn Pro Gln Glu Ser Leu Asp Arg Leu His 110 115 120 125 aag gtg aag act gtc tgc agc aag atc ctg gcc aat ttg gag caa ggc 495 Lys Val Lys Thr Val Cys Ser Lys Ile Leu Ala Asn Leu Glu Gln Gly 130 135 140 tta gca gaa gac ggc ggc atg agc agc gtg act cag gag ggc aga caa 543 Leu Ala Glu Asp Gly Gly Met Ser Ser Val Thr Gln Glu Gly Arg Gln 145 150 155 gcc tct atc cgg ctg tgg agg tca cgt ctg ggc cgg gtg atg tac tcc 591 Ala Ser Ile Arg Leu Trp Arg Ser Arg Leu Gly Arg Val Met Tyr Ser 160 165 170 atg gca aac tgt ctg ctc ctg atg aag gat tat gtg ctg gcc gtg gag 639 Met Ala Asn Cys Leu Leu Leu Met Lys Asp Tyr Val Leu Ala Val Glu 175 180 185 gcg tat cat tcg gtt atc aag tat tac cca gag caa gag ccc cag ctg 687 Ala Tyr His Ser Val Ile Lys Tyr Tyr Pro Glu Gln Glu Pro Gln Leu 190 195 200 205 ctc agc ggc atc ggc cgg att tcc ctg cag att gga gac ata aaa aca 735 Leu Ser Gly Ile Gly Arg Ile Ser Leu Gln Ile Gly Asp Ile Lys Thr 210 215 220 gct gaa aag tat ttt caa gac gtt gag aaa gta aca cag aaa tta gat 783 Ala Glu Lys Tyr Phe Gln Asp Val Glu Lys Val Thr Gln Lys Leu Asp 225 230 235 gga cta cag ggt aaa atc atg gtt ttg atg aac agc gcg ttc ctt cac 831 Gly Leu Gln Gly Lys Ile Met Val Leu Met Asn Ser Ala Phe Leu His 240 245 250 ctc ggg cag aat aac ttt gca gaa gcc cac agg ttc ttc aca gag atc 879 Leu Gly Gln Asn Asn Phe Ala Glu Ala His Arg Phe Phe Thr Glu Ile 255 260 265 tta agg atg gat cca aga aac gca gtg gcc aac aac aac gct gcc gtg 927 Leu Arg Met Asp Pro Arg Asn Ala Val Ala Asn Asn Asn Ala Ala Val 270 275 280 285 tgt ctg ctc tac ctg ggc aag ctc aag gac tcc ctg cgg cag ctg gag 975 Cys Leu Leu Tyr Leu Gly Lys Leu Lys Asp Ser Leu Arg Gln Leu Glu 290 295 300 gcc atg gtc cag cag gac ccc agg cac tac ctg cac gag agc gtg ctc 1023 Ala Met Val Gln Gln Asp Pro Arg His Tyr Leu His Glu Ser Val Leu 305 310 315 ttc aac ctg acc acc atg tac gag ctg gag tcc tca cgg agc atg cag 1071 Phe Asn Leu Thr Thr Met Tyr Glu Leu Glu Ser Ser Arg Ser Met Gln 320 325 330 aag aaa cag gcc ctg ctg gag gct gtc gcc ggc aag gag ggg gac agc 1119 Lys Lys Gln Ala Leu Leu Glu Ala Val Ala Gly Lys Glu Gly Asp Ser 335 340 345 ttc aac aca cag tgc ctc aag ctg gcc tagctgcctc caacacacta 1166 Phe Asn Thr Gln Cys Leu Lys Leu Ala 350 355 cgtcagaagg acccgggtct ttgaaactgt gtcttgaagc taatgtatta atgtgacatg 1226 gaggaactca ataaaactcc tgcttcactg gtgtctgctg cgtgtcttct tggtcccaag 1286 ccacggccca gcccaggact tccccgcagt tggtcggcgt tcagccacgc agtccctgca 1346 gctgggtcac tgttcatga 1365 40 358 PRT Homo sapiens 40 Met Pro Gly Leu Arg Phe Asp Asn Ile Gln Gly Asp Ala Val Lys Asp 1 5 10 15 Leu Met Leu Arg Phe Leu Gly Glu Lys Ala Ala Ala Lys Arg Gln Val 20 25 30 Leu Asn Ala Asp Ser Val Glu Gln Ser Phe Val Gly Leu Lys Gln Leu 35 40 45 Ile Leu Trp Phe Val Arg Leu Ala Leu Leu Val Lys Leu Gly Leu Phe 50 55 60 Gln Asn Ala Glu Met Glu Phe Glu Pro Phe Gly Asn Leu Asp Gln Pro 65 70 75 80 Asp Leu Tyr Tyr Glu Tyr Tyr Pro His Val Tyr Pro Gly Arg Arg Gly 85 90 95 Ser Met Val Pro Phe Ser Met Arg Ile Leu His Ala Glu Leu Gln Gln 100 105 110 Tyr Leu Gly Asn Pro Gln Glu Ser Leu Asp Arg Leu His Lys Val Lys 115 120 125 Thr Val Cys Ser Lys Ile Leu Ala Asn Leu Glu Gln Gly Leu Ala Glu 130 135 140 Asp Gly Gly Met Ser Ser Val Thr Gln Glu Gly Arg Gln Ala Ser Ile 145 150 155 160 Arg Leu Trp Arg Ser Arg Leu Gly Arg Val Met Tyr Ser Met Ala Asn 165 170 175 Cys Leu Leu Leu Met Lys Asp Tyr Val Leu Ala Val Glu Ala Tyr His 180 185 190 Ser Val Ile Lys Tyr Tyr Pro Glu Gln Glu Pro Gln Leu Leu Ser Gly 195 200 205 Ile Gly Arg Ile Ser Leu Gln Ile Gly Asp Ile Lys Thr Ala Glu Lys 210 215 220 Tyr Phe Gln Asp Val Glu Lys Val Thr Gln Lys Leu Asp Gly Leu Gln 225 230 235 240 Gly Lys Ile Met Val Leu Met Asn Ser Ala Phe Leu His Leu Gly Gln 245 250 255 Asn Asn Phe Ala Glu Ala His Arg Phe Phe Thr Glu Ile Leu Arg Met 260 265 270 Asp Pro Arg Asn Ala Val Ala Asn Asn Asn Ala Ala Val Cys Leu Leu 275 280 285 Tyr Leu Gly Lys Leu Lys Asp Ser Leu Arg Gln Leu Glu Ala Met Val 290 295 300 Gln Gln Asp Pro Arg His Tyr Leu His Glu Ser Val Leu Phe Asn Leu 305 310 315 320 Thr Thr Met Tyr Glu Leu Glu Ser Ser Arg Ser Met Gln Lys Lys Gln 325 330 335 Ala Leu Leu Glu Ala Val Ala Gly Lys Glu Gly Asp Ser Phe Asn Thr 340 345 350 Gln Cys Leu Lys Leu Ala 355 41 3462 DNA Homo sapiens CDS (2)..(3442) 41 g atg ggg cca gaa cgg aca ggg gcc gcg ccg ctg ccg ctg ctg ctg gtg 49 Met Gly Pro Glu Arg Thr Gly Ala Ala Pro Leu Pro Leu Leu Leu Val 1 5 10 15 tta gcg ctc agt caa ggc att tta aat tgt tgt ttg gcc tac aat gtt 97 Leu Ala Leu Ser Gln Gly Ile Leu Asn Cys Cys Leu Ala Tyr Asn Val 20 25 30 ggt ctc cca gaa gca aaa ata ttt tcc ggt cct tca agt gaa cag ttt 145 Gly Leu Pro Glu Ala Lys Ile Phe Ser Gly Pro Ser Ser Glu Gln Phe 35 40 45 ggc tat gca gtg cag cag ttt ata aat cca aaa ggc aac tgg tta ctg 193 Gly Tyr Ala Val Gln Gln Phe Ile Asn Pro Lys Gly Asn Trp Leu Leu 50 55 60 gtt ggt tca ccc tgg agt ggc ttt cct gag aac cga atg gga gat gtg 241 Val Gly Ser Pro Trp Ser Gly Phe Pro Glu Asn Arg Met Gly Asp Val 65 70 75 80 tat aaa tgt cct gtt gac cta tcc act gcc aca tgt gaa aaa cta aat 289 Tyr Lys Cys Pro Val Asp Leu Ser Thr Ala Thr Cys Glu Lys Leu Asn 85 90 95 ttg caa act tca aca agc att cca aat gtt act gag atg aaa acc aac 337 Leu Gln Thr Ser Thr Ser Ile Pro Asn Val Thr Glu Met Lys Thr Asn 100 105 110 atg agc ctc ggc ttg atc ctc acc agg aac atg gga act gga ggt ttt 385 Met Ser Leu Gly Leu Ile Leu Thr Arg Asn Met Gly Thr Gly Gly Phe 115 120 125 ctc aca tgt ggt cct ctg tgg gca cag caa tgt ggg aat cag tat tac 433 Leu Thr Cys Gly Pro Leu Trp Ala Gln Gln Cys Gly Asn Gln Tyr Tyr 130 135 140 aca acg ggt gtg tgt tct gac atc agt cct gat ttt cag ctc tca gcc 481 Thr Thr Gly Val Cys Ser Asp Ile Ser Pro Asp Phe Gln Leu Ser Ala 145 150 155 160 agc ttc tca cct gca act cag ccc tgc cct tcc ctc ata gat gtt gtg 529 Ser Phe Ser Pro Ala Thr Gln Pro Cys Pro Ser Leu Ile Asp Val Val 165 170 175 gtt gtg tgt gat gaa tca aat agt att tat cct tgg gat gca gta aag 577 Val Val Cys Asp Glu Ser Asn Ser Ile Tyr Pro Trp Asp Ala Val Lys 180 185 190 aat ttt ttg gaa aaa ttt gta caa ggc ctg gat ata ggc ccc aca aag 625 Asn Phe Leu Glu Lys Phe Val Gln Gly Leu Asp Ile Gly Pro Thr Lys 195 200 205 aca cag gtg ggg tta att cag tat gcc aat aat cca aga gtt gtg ttt 673 Thr Gln Val Gly Leu Ile Gln Tyr Ala Asn Asn Pro Arg Val Val Phe 210 215 220 aac ttg aac aca tat aaa acc aaa gaa gaa atg att gta gca aca tcc 721 Asn Leu Asn Thr Tyr Lys Thr Lys Glu Glu Met Ile Val Ala Thr Ser 225 230 235 240 cag aca tcc caa tat ggt ggg gac ctc aca aac aca ttc gga gca att 769 Gln Thr Ser Gln Tyr Gly Gly Asp Leu Thr Asn Thr Phe Gly Ala Ile 245 250 255 caa tat gca aga aaa tat gct tat tca gca gct tct ggt ggg cga cga 817 Gln Tyr Ala Arg Lys Tyr Ala Tyr Ser Ala Ala Ser Gly Gly Arg Arg 260 265 270 agt gct acg aaa gta atg gta gtt gta act gac ggt gaa tca cat gat 865 Ser Ala Thr Lys Val Met Val Val Val Thr Asp Gly Glu Ser His Asp 275 280 285 ggt tca atg ttg aaa gct gtg att gat caa tgc aac cat gac aat ata 913 Gly Ser Met Leu Lys Ala Val Ile Asp Gln Cys Asn His Asp Asn Ile 290 295 300 ctg agg ttt ggc ata gca gtt ctt ggg tac tta aac aga aac gcc ctt 961 Leu Arg Phe Gly Ile Ala Val Leu Gly Tyr Leu Asn Arg Asn Ala Leu 305 310 315 320 gat act aaa aat tta ata aaa gaa ata aaa gca atc gct agt att cca 1009 Asp Thr Lys Asn Leu Ile Lys Glu Ile Lys Ala Ile Ala Ser Ile Pro 325 330 335 aca gaa aga tac ttt ttc aat gtg tct gat gaa gca gct cta cta gaa 1057 Thr Glu Arg Tyr Phe Phe Asn Val Ser Asp Glu Ala Ala Leu Leu Glu 340 345 350 aag gct ggg aca tta gga gaa caa att ttc agc att gaa ggt act gtt 1105 Lys Ala Gly Thr Leu Gly Glu Gln Ile Phe Ser Ile Glu Gly Thr Val 355 360 365 caa gga gga gac aac ttt cag atg gaa atg tca caa gtg gga ttc agt 1153 Gln Gly Gly Asp Asn Phe Gln Met Glu Met Ser Gln Val Gly Phe Ser 370 375 380 gca gat tac tct tct caa aat gat att ctg atg ctg ggt gca gtg gga 1201 Ala Asp Tyr Ser Ser Gln Asn Asp Ile Leu Met Leu Gly Ala Val Gly 385 390 395 400 gct ttt ggc tgg agt ggg acc att gtc cag aag aca tct cat ggc cat 1249 Ala Phe Gly Trp Ser Gly Thr Ile Val Gln Lys Thr Ser His Gly His 405 410 415 ttg atc ttt cct aaa caa gcc ttt gac caa att ctg cag gac aga aat 1297 Leu Ile Phe Pro Lys Gln Ala Phe Asp Gln Ile Leu Gln Asp Arg Asn 420 425 430 cac agt tca tat tta ggt tac tct gtg gct gca att tct act gga gaa 1345 His Ser Ser Tyr Leu Gly Tyr Ser Val Ala Ala Ile Ser Thr Gly Glu 435 440 445 agc act cac ttt gtt gct ggt gct cct cgg gca aat tat acc ggc cag 1393 Ser Thr His Phe Val Ala Gly Ala Pro Arg Ala Asn Tyr Thr Gly Gln 450 455 460 ata gtg cta tat agt gtg aat gag aat ggc aat atc acg gtt att cag 1441 Ile Val Leu Tyr Ser Val Asn Glu Asn Gly Asn Ile Thr Val Ile Gln 465 470 475 480 gct cac cga ggt gac cag att ggc tcc tat ttt ggt agt gtg ctg tgt 1489 Ala His Arg Gly Asp Gln Ile Gly Ser Tyr Phe Gly Ser Val Leu Cys 485 490 495 tca gtt gat gtg gat aaa gac acc att aca gac gtg ctc ttg gta ggt 1537 Ser Val Asp Val Asp Lys Asp Thr Ile Thr Asp Val Leu Leu Val Gly 500 505 510 gca cca atg tac atg agt gac cta aag aaa gag gaa gga aga gtc tac 1585 Ala Pro Met Tyr Met Ser Asp Leu Lys Lys Glu Glu Gly Arg Val Tyr 515 520 525 ctg ttt act atc aaa gag ggc att ttg ggt cag cac caa ttt ctt gaa 1633 Leu Phe Thr Ile Lys Glu Gly Ile Leu Gly Gln His Gln Phe Leu Glu 530 535 540 ggc ccc gag ggc att gaa aac act cga ttt ggt tca gca att gca gct 1681 Gly Pro Glu Gly Ile Glu Asn Thr Arg Phe Gly Ser Ala Ile Ala Ala 545 550 555 560 ctt tca gac atc aac atg gat ggc ttt aat gat gtg att gtt ggt tca 1729 Leu Ser Asp Ile Asn Met Asp Gly Phe Asn Asp Val Ile Val Gly Ser 565 570 575 cca cta gaa aat cag aat tct gga gct gta tac att tac aat ggt cat 1777 Pro Leu Glu Asn Gln Asn Ser Gly Ala Val Tyr Ile Tyr Asn Gly His 580 585 590 cag ggc act atc cgc aca aag tat tcc cag aaa atc ttg gga tcc gat 1825 Gln Gly Thr Ile Arg Thr Lys Tyr Ser Gln Lys Ile Leu Gly Ser Asp 595 600 605 gga gcc ttt agg agc cat ctc cag tac ttt ggg agg tcc ttg gat ggc 1873 Gly Ala Phe Arg Ser His Leu Gln Tyr Phe Gly Arg Ser Leu Asp Gly 610 615 620 tat gga gat tta aat ggg gat tcc atc acc gat gtg tct att ggt gcc 1921 Tyr Gly Asp Leu Asn Gly Asp Ser Ile Thr Asp Val Ser Ile Gly Ala 625 630 635 640 ttt gga caa gtg gtt caa ctc tgg tca caa agt att gct gat gta gct 1969 Phe Gly Gln Val Val Gln Leu Trp Ser Gln Ser Ile Ala Asp Val Ala 645 650 655 ata gaa gct tca ttc aca cca gaa aaa atc act ttg gtc aac aag aat 2017 Ile Glu Ala Ser Phe Thr Pro Glu Lys Ile Thr Leu Val Asn Lys Asn 660 665 670 gct cag ata att ctc aaa ctc tgc ttc agt gca aag ttc aga cct act 2065 Ala Gln Ile Ile Leu Lys Leu Cys Phe Ser Ala Lys Phe Arg Pro Thr 675 680 685 aag caa aac aat caa gtg gcc att gta tat aac atc aca ctt gat gca 2113 Lys Gln Asn Asn Gln Val Ala Ile Val Tyr Asn Ile Thr Leu Asp Ala 690 695 700 gat gga ttt tca tcc aga gta acc tcc agg ggg tta ttt aaa gaa aac 2161 Asp Gly Phe Ser Ser Arg Val Thr Ser Arg Gly Leu Phe Lys Glu Asn 705 710 715 720 aat gaa agg tgc ctg cag aag aat atg gta gta aat caa gca cag agt 2209 Asn Glu Arg Cys Leu Gln Lys Asn Met Val Val Asn Gln Ala Gln Ser 725 730 735 tgc ccc gag cac atc att tat ata cag gag ccc tct gat gtt gtc aac 2257 Cys Pro Glu His Ile Ile Tyr Ile Gln Glu Pro Ser Asp Val Val Asn 740 745 750 tct ttg gat ttg cgt gtg gac atc agt ctg gaa aac cct ggc act agc 2305 Ser Leu Asp Leu Arg Val Asp Ile Ser Leu Glu Asn Pro Gly Thr Ser 755 760 765 cct gcc ctt gaa gcc tat tct gag act gcc aag gtc ttc agt att cct 2353 Pro Ala Leu Glu Ala Tyr Ser Glu Thr Ala Lys Val Phe Ser Ile Pro 770 775 780 ttc cac aaa gac tgt ggt gag gac gga ctt tgc att tct gat cta gtc 2401 Phe His Lys Asp Cys Gly Glu Asp Gly Leu Cys Ile Ser Asp Leu Val 785 790 795 800 cta gat gtc cga caa ata cca gct gct caa gaa caa ccc ttt att gtc 2449 Leu Asp Val Arg Gln Ile Pro Ala Ala Gln Glu Gln Pro Phe Ile Val 805 810 815 agc aac caa aac aaa agg tta aca ttt tca gta acg ctg aaa aat aaa 2497 Ser Asn Gln Asn Lys Arg Leu Thr Phe Ser Val Thr Leu Lys Asn Lys 820 825 830 agg gaa agt gca tac aac act gga att gtt gtt gat ttt tca gaa aac 2545 Arg Glu Ser Ala Tyr Asn Thr Gly Ile Val Val Asp Phe Ser Glu Asn 835 840 845 ttg ttt ttt gca tca ttc tcc ctg ccg gtt gat ggg aca gaa gta aca 2593 Leu Phe Phe Ala Ser Phe Ser Leu Pro Val Asp Gly Thr Glu Val Thr 850 855 860 tgc cag gtg gct gca tct cag aag tct gtt gcc tgc gat gta ggc tac 2641 Cys Gln Val Ala Ala Ser Gln Lys Ser Val Ala Cys Asp Val Gly Tyr 865 870 875 880 cct gct tta aag aga gaa caa cag gtg act ttt act att aac ttt gac 2689 Pro Ala Leu Lys Arg Glu Gln Gln Val Thr Phe Thr Ile Asn Phe Asp 885 890 895 ttc aat ctt caa aac ctt cag aat cag gcg tct ctc agt ttc cag gcc 2737 Phe Asn Leu Gln Asn Leu Gln Asn Gln Ala Ser Leu Ser Phe Gln Ala 900 905 910 tta agt gaa agc caa gaa gaa aac aag gct gat aat ttg gtc aac ctc 2785 Leu Ser Glu Ser Gln Glu Glu Asn Lys Ala Asp Asn Leu Val Asn Leu 915 920 925 aaa att cct ctc ctg tat gat gct gaa att cac tta aca aag gta aca 2833 Lys Ile Pro Leu Leu Tyr Asp Ala Glu Ile His Leu Thr Lys Val Thr 930 935 940 aca gga agt gtt cca gta agc atg gca act gta atc atc cac atc cct 2881 Thr Gly Ser Val Pro Val Ser Met Ala Thr Val Ile Ile His Ile Pro 945 950 955 960 cag tat acc aaa gaa aag aac cca ctg atg tac cta act ggg gtg caa 2929 Gln Tyr Thr Lys Glu Lys Asn Pro Leu Met Tyr Leu Thr Gly Val Gln 965 970 975 aca gac aag gct ggt gac atc agt tgt aat gca gat atc aat cca ctg 2977 Thr Asp Lys Ala Gly Asp Ile Ser Cys Asn Ala Asp Ile Asn Pro Leu 980 985 990 aaa ata gga caa aca tct tct tct gta tct ttc aaa agt gaa aat ttc 3025 Lys Ile Gly Gln Thr Ser Ser Ser Val Ser Phe Lys Ser Glu Asn Phe 995 1000 1005 agg cac acc aaa gaa ttg aac tgc aga act gct tcc tgt agt aat gtt 3073 Arg His Thr Lys Glu Leu Asn Cys Arg Thr Ala Ser Cys Ser Asn Val 1010 1015 1020 acc tgc tgg ttg aaa gac gtt cac atg aaa gga gaa tac ttt gtt aat 3121 Thr Cys Trp Leu Lys Asp Val His Met Lys Gly Glu Tyr Phe Val Asn 1025 1030 1035 1040 gtg act acc aga att tgg aac ggg act ttc gca tca tca acg ttc cag 3169 Val Thr Thr Arg Ile Trp Asn Gly Thr Phe Ala Ser Ser Thr Phe Gln 1045 1050 1055 aca gta cag cta acg gca gct gca gaa atc aac acc tat aac cct gag 3217 Thr Val Gln Leu Thr Ala Ala Ala Glu Ile Asn Thr Tyr Asn Pro Glu 1060 1065 1070 ata tat gtg att gaa gat aac act gtt acg att ccc ctg atg ata atg 3265 Ile Tyr Val Ile Glu Asp Asn Thr Val Thr Ile Pro Leu Met Ile Met 1075 1080 1085 aaa cct gat gag aaa gcc gaa gta cca aca gga gtt ata ata gga agt 3313 Lys Pro Asp Glu Lys Ala Glu Val Pro Thr Gly Val Ile Ile Gly Ser 1090 1095 1100 ata att gct gga atc ctt ttg ctg tta gct ctg gtt gca att tta tgg 3361 Ile Ile Ala Gly Ile Leu Leu Leu Leu Ala Leu Val Ala Ile Leu Trp 1105 1110 1115 1120 aag ctc ggc ttc ttc aaa aga aaa tat gaa aag atg acc aaa aat cca 3409 Lys Leu Gly Phe Phe Lys Arg Lys Tyr Glu Lys Met Thr Lys Asn Pro 1125 1130 1135 gat gag att gat gag acc aca gag ctc agt agc tgaaccagca gacctacctg 3462 Asp Glu Ile Asp Glu Thr Thr Glu Leu Ser Ser 1140 1145 42 1147 PRT Homo sapiens 42 Met Gly Pro Glu Arg Thr Gly Ala Ala Pro Leu Pro Leu Leu Leu Val 1 5 10 15 Leu Ala Leu Ser Gln Gly Ile Leu Asn Cys Cys Leu Ala Tyr Asn Val 20 25 30 Gly Leu Pro Glu Ala Lys Ile Phe Ser Gly Pro Ser Ser Glu Gln Phe 35 40 45 Gly Tyr Ala Val Gln Gln Phe Ile Asn Pro Lys Gly Asn Trp Leu Leu 50 55 60 Val Gly Ser Pro Trp Ser Gly Phe Pro Glu Asn Arg Met Gly Asp Val 65 70 75 80 Tyr Lys Cys Pro Val Asp Leu Ser Thr Ala Thr Cys Glu Lys Leu Asn 85 90 95 Leu Gln Thr Ser Thr Ser Ile Pro Asn Val Thr Glu Met Lys Thr Asn 100 105 110 Met Ser Leu Gly Leu Ile Leu Thr Arg Asn Met Gly Thr Gly Gly Phe 115 120 125 Leu Thr Cys Gly Pro Leu Trp Ala Gln Gln Cys Gly Asn Gln Tyr Tyr 130 135 140 Thr Thr Gly Val Cys Ser Asp Ile Ser Pro Asp Phe Gln Leu Ser Ala 145 150 155 160 Ser Phe Ser Pro Ala Thr Gln Pro Cys Pro Ser Leu Ile Asp Val Val 165 170 175 Val Val Cys Asp Glu Ser Asn Ser Ile Tyr Pro Trp Asp Ala Val Lys 180 185 190 Asn Phe Leu Glu Lys Phe Val Gln Gly Leu Asp Ile Gly Pro Thr Lys 195 200 205 Thr Gln Val Gly Leu Ile Gln Tyr Ala Asn Asn Pro Arg Val Val Phe 210 215 220 Asn Leu Asn Thr Tyr Lys Thr Lys Glu Glu Met Ile Val Ala Thr Ser 225 230 235 240 Gln Thr Ser Gln Tyr Gly Gly Asp Leu Thr Asn Thr Phe Gly Ala Ile 245 250 255 Gln Tyr Ala Arg Lys Tyr Ala Tyr Ser Ala Ala Ser Gly Gly Arg Arg 260 265 270 Ser Ala Thr Lys Val Met Val Val Val Thr Asp Gly Glu Ser His Asp 275 280 285 Gly Ser Met Leu Lys Ala Val Ile Asp Gln Cys Asn His Asp Asn Ile 290 295 300 Leu Arg Phe Gly Ile Ala Val Leu Gly Tyr Leu Asn Arg Asn Ala Leu 305 310 315 320 Asp Thr Lys Asn Leu Ile Lys Glu Ile Lys Ala Ile Ala Ser Ile Pro 325 330 335 Thr Glu Arg Tyr Phe Phe Asn Val Ser Asp Glu Ala Ala Leu Leu Glu 340 345 350 Lys Ala Gly Thr Leu Gly Glu Gln Ile Phe Ser Ile Glu Gly Thr Val 355 360 365 Gln Gly Gly Asp Asn Phe Gln Met Glu Met Ser Gln Val Gly Phe Ser 370 375 380 Ala Asp Tyr Ser Ser Gln Asn Asp Ile Leu Met Leu Gly Ala Val Gly 385 390 395 400 Ala Phe Gly Trp Ser Gly Thr Ile Val Gln Lys Thr Ser His Gly His 405 410 415 Leu Ile Phe Pro Lys Gln Ala Phe Asp Gln Ile Leu Gln Asp Arg Asn 420 425 430 His Ser Ser Tyr Leu Gly Tyr Ser Val Ala Ala Ile Ser Thr Gly Glu 435 440 445 Ser Thr His Phe Val Ala Gly Ala Pro Arg Ala Asn Tyr Thr Gly Gln 450 455 460 Ile Val Leu Tyr Ser Val Asn Glu Asn Gly Asn Ile Thr Val Ile Gln 465 470 475 480 Ala His Arg Gly Asp Gln Ile Gly Ser Tyr Phe Gly Ser Val Leu Cys 485 490 495 Ser Val Asp Val Asp Lys Asp Thr Ile Thr Asp Val Leu Leu Val Gly 500 505 510 Ala Pro Met Tyr Met Ser Asp Leu Lys Lys Glu Glu Gly Arg Val Tyr 515 520 525 Leu Phe Thr Ile Lys Glu Gly Ile Leu Gly Gln His Gln Phe Leu Glu 530 535 540 Gly Pro Glu Gly Ile Glu Asn Thr Arg Phe Gly Ser Ala Ile Ala Ala 545 550 555 560 Leu Ser Asp Ile Asn Met Asp Gly Phe Asn Asp Val Ile Val Gly Ser 565 570 575 Pro Leu Glu Asn Gln Asn Ser Gly Ala Val Tyr Ile Tyr Asn Gly His 580 585 590 Gln Gly Thr Ile Arg Thr Lys Tyr Ser Gln Lys Ile Leu Gly Ser Asp 595 600 605 Gly Ala Phe Arg Ser His Leu Gln Tyr Phe Gly Arg Ser Leu Asp Gly 610 615 620 Tyr Gly Asp Leu Asn Gly Asp Ser Ile Thr Asp Val Ser Ile Gly Ala 625 630 635 640 Phe Gly Gln Val Val Gln Leu Trp Ser Gln Ser Ile Ala Asp Val Ala 645 650 655 Ile Glu Ala Ser Phe Thr Pro Glu Lys Ile Thr Leu Val Asn Lys Asn 660 665 670 Ala Gln Ile Ile Leu Lys Leu Cys Phe Ser Ala Lys Phe Arg Pro Thr 675 680 685 Lys Gln Asn Asn Gln Val Ala Ile Val Tyr Asn Ile Thr Leu Asp Ala 690 695 700 Asp Gly Phe Ser Ser Arg Val Thr Ser Arg Gly Leu Phe Lys Glu Asn 705 710 715 720 Asn Glu Arg Cys Leu Gln Lys Asn Met Val Val Asn Gln Ala Gln Ser 725 730 735 Cys Pro Glu His Ile Ile Tyr Ile Gln Glu Pro Ser Asp Val Val Asn 740 745 750 Ser Leu Asp Leu Arg Val Asp Ile Ser Leu Glu Asn Pro Gly Thr Ser 755 760 765 Pro Ala Leu Glu Ala Tyr Ser Glu Thr Ala Lys Val Phe Ser Ile Pro 770 775 780 Phe His Lys Asp Cys Gly Glu Asp Gly Leu Cys Ile Ser Asp Leu Val 785 790 795 800 Leu Asp Val Arg Gln Ile Pro Ala Ala Gln Glu Gln Pro Phe Ile Val 805 810 815 Ser Asn Gln Asn Lys Arg Leu Thr Phe Ser Val Thr Leu Lys Asn Lys 820 825 830 Arg Glu Ser Ala Tyr Asn Thr Gly Ile Val Val Asp Phe Ser Glu Asn 835 840 845 Leu Phe Phe Ala Ser Phe Ser Leu Pro Val Asp Gly Thr Glu Val Thr 850 855 860 Cys Gln Val Ala Ala Ser Gln Lys Ser Val Ala Cys Asp Val Gly Tyr 865 870 875 880 Pro Ala Leu Lys Arg Glu Gln Gln Val Thr Phe Thr Ile Asn Phe Asp 885 890 895 Phe Asn Leu Gln Asn Leu Gln Asn Gln Ala Ser Leu Ser Phe Gln Ala 900 905 910 Leu Ser Glu Ser Gln Glu Glu Asn Lys Ala Asp Asn Leu Val Asn Leu 915 920 925 Lys Ile Pro Leu Leu Tyr Asp Ala Glu Ile His Leu Thr Lys Val Thr 930 935 940 Thr Gly Ser Val Pro Val Ser Met Ala Thr Val Ile Ile His Ile Pro 945 950 955 960 Gln Tyr Thr Lys Glu Lys Asn Pro Leu Met Tyr Leu Thr Gly Val Gln 965 970 975 Thr Asp Lys Ala Gly Asp Ile Ser Cys Asn Ala Asp Ile Asn Pro Leu 980 985 990 Lys Ile Gly Gln Thr Ser Ser Ser Val Ser Phe Lys Ser Glu Asn Phe 995 1000 1005 Arg His Thr Lys Glu Leu Asn Cys Arg Thr Ala Ser Cys Ser Asn Val 1010 1015 1020 Thr Cys Trp Leu Lys Asp Val His Met Lys Gly Glu Tyr Phe Val Asn 1025 1030 1035 1040 Val Thr Thr Arg Ile Trp Asn Gly Thr Phe Ala Ser Ser Thr Phe Gln 1045 1050 1055 Thr Val Gln Leu Thr Ala Ala Ala Glu Ile Asn Thr Tyr Asn Pro Glu 1060 1065 1070 Ile Tyr Val Ile Glu Asp Asn Thr Val Thr Ile Pro Leu Met Ile Met 1075 1080 1085 Lys Pro Asp Glu Lys Ala Glu Val Pro Thr Gly Val Ile Ile Gly Ser 1090 1095 1100 Ile Ile Ala Gly Ile Leu Leu Leu Leu Ala Leu Val Ala Ile Leu Trp 1105 1110 1115 1120 Lys Leu Gly Phe Phe Lys Arg Lys Tyr Glu Lys Met Thr Lys Asn Pro 1125 1130 1135 Asp Glu Ile Asp Glu Thr Thr Glu Leu Ser Ser 1140 1145 43 1105 DNA Homo sapiens CDS (61)..(1044) 43 aggaggaaaa acaagtgtgt gttgggggga acagggggaa aagcattttt ggtggatggt 60 atg aag cca gcc atg gaa act gca gcc gag gaa aat act gaa caa agc 108 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 caa gag aga aaa gtg aac agc aga gct gaa atg gaa att ggc agg tac 156 Gln Glu Arg Lys Val Asn Ser Arg Ala Glu Met Glu Ile Gly Arg Tyr 20 25 30 cac tgg atg tac cca ggc tca aag aac cac cag tac cat ccc gtg cca 204 His Trp Met Tyr Pro Gly Ser Lys Asn His Gln Tyr His Pro Val Pro 35 40 45 acc ctg ggg gac agg gct agc ccc ttg agc agt cca ggc tgc ttt gaa 252 Thr Leu Gly Asp Arg Ala Ser Pro Leu Ser Ser Pro Gly Cys Phe Glu 50 55 60 tgc tgc atc aag tgt ctg gga gga gtc ccc tac gcc tcc ctg gtg gcc 300 Cys Cys Ile Lys Cys Leu Gly Gly Val Pro Tyr Ala Ser Leu Val Ala 65 70 75 80 acc atc ctc tgc ttc tcc ggg gtg gcc tta ttc tgc ggc tgt ggg cat 348 Thr Ile Leu Cys Phe Ser Gly Val Ala Leu Phe Cys Gly Cys Gly His 85 90 95 gtg gct ctc gca ggc acc gtg gcg att ctt gag caa cac ttc tcc acc 396 Val Ala Leu Ala Gly Thr Val Ala Ile Leu Glu Gln His Phe Ser Thr 100 105 110 aac gcc agt gac cat gcc ttg ctg agc gag gtg ata caa ctg atg cag 444 Asn Ala Ser Asp His Ala Leu Leu Ser Glu Val Ile Gln Leu Met Gln 115 120 125 tat gtc atc tat gga att gcg tcc ttt ttc ttc ttg tat ggg atc att 492 Tyr Val Ile Tyr Gly Ile Ala Ser Phe Phe Phe Leu Tyr Gly Ile Ile 130 135 140 ctg ttg gca gaa ggc ttt tac acc aca agt gca gtg aaa gaa ctg cac 540 Leu Leu Ala Glu Gly Phe Tyr Thr Thr Ser Ala Val Lys Glu Leu His 145 150 155 160 ggt gag ttt aaa aca acc gct tgt ggc cga tgc atc agt gga atg ttc 588 Gly Glu Phe Lys Thr Thr Ala Cys Gly Arg Cys Ile Ser Gly Met Phe 165 170 175 gtt ttc ctc acc tat gtg ctt gga gtg gcc tgg ctg ggt gtg ttt ggt 636 Val Phe Leu Thr Tyr Val Leu Gly Val Ala Trp Leu Gly Val Phe Gly 180 185 190 ttc tca gcg gtg ccc gtg ttt atg ttc tac aac ata tgg tca act tgt 684 Phe Ser Ala Val Pro Val Phe Met Phe Tyr Asn Ile Trp Ser Thr Cys 195 200 205 gaa gtc atc aag tca ccg cag acc aac ggg acc acg ggt gtg gag cag 732 Glu Val Ile Lys Ser Pro Gln Thr Asn Gly Thr Thr Gly Val Glu Gln 210 215 220 atc tgt gtg gat atc cga caa tac ggt atc att cct tgg aat gct ttc 780 Ile Cys Val Asp Ile Arg Gln Tyr Gly Ile Ile Pro Trp Asn Ala Phe 225 230 235 240 ccc gga aaa ata tgt ggc tct gcc ctg gag aac atc tgc aac aca aac 828 Pro Gly Lys Ile Cys Gly Ser Ala Leu Glu Asn Ile Cys Asn Thr Asn 245 250 255 gag ttc tac atg tcc tat cac ctg ttc att gtg gcc tgt gca gga gct 876 Glu Phe Tyr Met Ser Tyr His Leu Phe Ile Val Ala Cys Ala Gly Ala 260 265 270 ggt gcc acc gtc att gcc ctg atc cac ttc ctc atg ata ctg tct tct 924 Gly Ala Thr Val Ile Ala Leu Ile His Phe Leu Met Ile Leu Ser Ser 275 280 285 aac tgg gct tac tta aag gat gcg agc aaa atg cag gct tac cag gat 972 Asn Trp Ala Tyr Leu Lys Asp Ala Ser Lys Met Gln Ala Tyr Gln Asp 290 295 300 atc aaa gca aag gaa gaa cag gaa ctg caa gat atc cag tct cgg tca 1020 Ile Lys Ala Lys Glu Glu Gln Glu Leu Gln Asp Ile Gln Ser Arg Ser 305 310 315 320 aaa gaa caa ctc aat tct tac aca taaatgtttg ccagagtgtt tcggccgacg 1074 Lys Glu Gln Leu Asn Ser Tyr Thr 325 tatttacagc tctgacaaat catcagacag c 1105 44 328 PRT Homo sapiens 44 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 Gln Glu Arg Lys Val Asn Ser Arg Ala Glu Met Glu Ile Gly Arg Tyr 20 25 30 His Trp Met Tyr Pro Gly Ser Lys Asn His Gln Tyr His Pro Val Pro 35 40 45 Thr Leu Gly Asp Arg Ala Ser Pro Leu Ser Ser Pro Gly Cys Phe Glu 50 55 60 Cys Cys Ile Lys Cys Leu Gly Gly Val Pro Tyr Ala Ser Leu Val Ala 65 70 75 80 Thr Ile Leu Cys Phe Ser Gly Val Ala Leu Phe Cys Gly Cys Gly His 85 90 95 Val Ala Leu Ala Gly Thr Val Ala Ile Leu Glu Gln His Phe Ser Thr 100 105 110 Asn Ala Ser Asp His Ala Leu Leu Ser Glu Val Ile Gln Leu Met Gln 115 120 125 Tyr Val Ile Tyr Gly Ile Ala Ser Phe Phe Phe Leu Tyr Gly Ile Ile 130 135 140 Leu Leu Ala Glu Gly Phe Tyr Thr Thr Ser Ala Val Lys Glu Leu His 145 150 155 160 Gly Glu Phe Lys Thr Thr Ala Cys Gly Arg Cys Ile Ser Gly Met Phe 165 170 175 Val Phe Leu Thr Tyr Val Leu Gly Val Ala Trp Leu Gly Val Phe Gly 180 185 190 Phe Ser Ala Val Pro Val Phe Met Phe Tyr Asn Ile Trp Ser Thr Cys 195 200 205 Glu Val Ile Lys Ser Pro Gln Thr Asn Gly Thr Thr Gly Val Glu Gln 210 215 220 Ile Cys Val Asp Ile Arg Gln Tyr Gly Ile Ile Pro Trp Asn Ala Phe 225 230 235 240 Pro Gly Lys Ile Cys Gly Ser Ala Leu Glu Asn Ile Cys Asn Thr Asn 245 250 255 Glu Phe Tyr Met Ser Tyr His Leu Phe Ile Val Ala Cys Ala Gly Ala 260 265 270 Gly Ala Thr Val Ile Ala Leu Ile His Phe Leu Met Ile Leu Ser Ser 275 280 285 Asn Trp Ala Tyr Leu Lys Asp Ala Ser Lys Met Gln Ala Tyr Gln Asp 290 295 300 Ile Lys Ala Lys Glu Glu Gln Glu Leu Gln Asp Ile Gln Ser Arg Ser 305 310 315 320 Lys Glu Gln Leu Asn Ser Tyr Thr 325 45 1133 DNA Homo sapiens CDS (61)..(975) 45 aggaggaaaa acaagtgtgt gttgggggga acagggggaa aagcattttt ggtggatggt 60 atg aag cca gcc atg gaa act gca gcc gag gaa aat act gaa caa agc 108 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 caa gag aga aaa gtg aac agc aga gct gaa atg gaa att ggc agg tac 156 Gln Glu Arg Lys Val Asn Ser Arg Ala Glu Met Glu Ile Gly Arg Tyr 20 25 30 cac tgg atg tac cca ggc tca aag aac cac cag tac cat ccc gtg cca 204 His Trp Met Tyr Pro Gly Ser Lys Asn His Gln Tyr His Pro Val Pro 35 40 45 acc ctg ggg gac agg gct agc ccc ttg agc agt cca ggc tgc ttt gaa 252 Thr Leu Gly Asp Arg Ala Ser Pro Leu Ser Ser Pro Gly Cys Phe Glu 50 55 60 tgc tgc atc aag tgt ctg gga gga gtc ccc tac gcc tcc ctg gtg gcc 300 Cys Cys Ile Lys Cys Leu Gly Gly Val Pro Tyr Ala Ser Leu Val Ala 65 70 75 80 acc atc ctc tgc ttc tcc ggg gtg gcc tta ttc tgc ggc tgt ggg cat 348 Thr Ile Leu Cys Phe Ser Gly Val Ala Leu Phe Cys Gly Cys Gly His 85 90 95 gtg gct ctc gca ggc acc gtg gcg att ctt gag caa cac ttc tcc acc 396 Val Ala Leu Ala Gly Thr Val Ala Ile Leu Glu Gln His Phe Ser Thr 100 105 110 aac gcc agt gac cat gcc ttg ctg agc gag gtg ata caa ctg atg cag 444 Asn Ala Ser Asp His Ala Leu Leu Ser Glu Val Ile Gln Leu Met Gln 115 120 125 tat gtc atc tat gga att gcg tcc ttt ttc ttc ttg tat ggg atc att 492 Tyr Val Ile Tyr Gly Ile Ala Ser Phe Phe Phe Leu Tyr Gly Ile Ile 130 135 140 ctg ttg gca gaa ggc ttt tac acc aca agt gca gtg aaa gaa ctg cac 540 Leu Leu Ala Glu Gly Phe Tyr Thr Thr Ser Ala Val Lys Glu Leu His 145 150 155 160 ggt gag ttt aaa aca acc gct tgt ggc cga tgc atc agt gga atg ttc 588 Gly Glu Phe Lys Thr Thr Ala Cys Gly Arg Cys Ile Ser Gly Met Phe 165 170 175 gtt ttc ctc acc tat gtg ctt gga gtg gcc tgg ctg ggt gtg ttt ggt 636 Val Phe Leu Thr Tyr Val Leu Gly Val Ala Trp Leu Gly Val Phe Gly 180 185 190 ttc tca gcg gtg ccc gtg ttt atg ttc tac aac ata tgg tca act tgt 684 Phe Ser Ala Val Pro Val Phe Met Phe Tyr Asn Ile Trp Ser Thr Cys 195 200 205 gaa gtc atc aag tca ccg cag acc aac ggg acc acg ggt gtg gag cag 732 Glu Val Ile Lys Ser Pro Gln Thr Asn Gly Thr Thr Gly Val Glu Gln 210 215 220 atc tgt gtg gat atc cga caa tac ggt atc att cct tgg aat gct ttc 780 Ile Cys Val Asp Ile Arg Gln Tyr Gly Ile Ile Pro Trp Asn Ala Phe 225 230 235 240 ccc gga aaa ata tgt ggc tct gcc ctg gag aac atc tgc aac aca aac 828 Pro Gly Lys Ile Cys Gly Ser Ala Leu Glu Asn Ile Cys Asn Thr Asn 245 250 255 gag ttc tac atg tcc tat cac ctg ttc att gtg gcc tgt gca gga gct 876 Glu Phe Tyr Met Ser Tyr His Leu Phe Ile Val Ala Cys Ala Gly Ala 260 265 270 ggt gcc acc gtc att gcc ctg ctg atc tac atg atg gct act aca tat 924 Gly Ala Thr Val Ile Ala Leu Leu Ile Tyr Met Met Ala Thr Thr Tyr 275 280 285 aac tat gcg gtt ttg aag ttt aag agt cgg gaa gat tgc tgc act aaa 972 Asn Tyr Ala Val Leu Lys Phe Lys Ser Arg Glu Asp Cys Cys Thr Lys 290 295 300 ttc taaattgcat aaggagtttt agagagctat gctctgtagc atgaaatatc 1025 Phe 305 actgacactc cagactaaag cagagtctag gtttctgcaa tttgttacag taatttgtaa 1085 tagctttgta actcacctgc atgtagataa taagatgact actgtaca 1133 46 305 PRT Homo sapiens 46 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 Gln Glu Arg Lys Val Asn Ser Arg Ala Glu Met Glu Ile Gly Arg Tyr 20 25 30 His Trp Met Tyr Pro Gly Ser Lys Asn His Gln Tyr His Pro Val Pro 35 40 45 Thr Leu Gly Asp Arg Ala Ser Pro Leu Ser Ser Pro Gly Cys Phe Glu 50 55 60 Cys Cys Ile Lys Cys Leu Gly Gly Val Pro Tyr Ala Ser Leu Val Ala 65 70 75 80 Thr Ile Leu Cys Phe Ser Gly Val Ala Leu Phe Cys Gly Cys Gly His 85 90 95 Val Ala Leu Ala Gly Thr Val Ala Ile Leu Glu Gln His Phe Ser Thr 100 105 110 Asn Ala Ser Asp His Ala Leu Leu Ser Glu Val Ile Gln Leu Met Gln 115 120 125 Tyr Val Ile Tyr Gly Ile Ala Ser Phe Phe Phe Leu Tyr Gly Ile Ile 130 135 140 Leu Leu Ala Glu Gly Phe Tyr Thr Thr Ser Ala Val Lys Glu Leu His 145 150 155 160 Gly Glu Phe Lys Thr Thr Ala Cys Gly Arg Cys Ile Ser Gly Met Phe 165 170 175 Val Phe Leu Thr Tyr Val Leu Gly Val Ala Trp Leu Gly Val Phe Gly 180 185 190 Phe Ser Ala Val Pro Val Phe Met Phe Tyr Asn Ile Trp Ser Thr Cys 195 200 205 Glu Val Ile Lys Ser Pro Gln Thr Asn Gly Thr Thr Gly Val Glu Gln 210 215 220 Ile Cys Val Asp Ile Arg Gln Tyr Gly Ile Ile Pro Trp Asn Ala Phe 225 230 235 240 Pro Gly Lys Ile Cys Gly Ser Ala Leu Glu Asn Ile Cys Asn Thr Asn 245 250 255 Glu Phe Tyr Met Ser Tyr His Leu Phe Ile Val Ala Cys Ala Gly Ala 260 265 270 Gly Ala Thr Val Ile Ala Leu Leu Ile Tyr Met Met Ala Thr Thr Tyr 275 280 285 Asn Tyr Ala Val Leu Lys Phe Lys Ser Arg Glu Asp Cys Cys Thr Lys 290 295 300 Phe 305 47 1182 DNA Homo sapiens CDS (61)..(924) 47 aggaggaaaa acaagtgtgt gttgggggga acagggggaa aagcattttt ggtggatggt 60 atg aag cca gcc atg gaa act gca gcc gag gaa aat act gaa caa agc 108 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 caa gag aga aaa ggc tgc ttt gaa tgc tgc atc aag tgt ctg gga gga 156 Gln Glu Arg Lys Gly Cys Phe Glu Cys Cys Ile Lys Cys Leu Gly Gly 20 25 30 gtc ccc tac gcc tcc ctg gtg gcc acc atc ctc tgc ttc tcc ggg gtg 204 Val Pro Tyr Ala Ser Leu Val Ala Thr Ile Leu Cys Phe Ser Gly Val 35 40 45 gcc tta ttc tgc ggc tgt ggg cat gtg gct ctc gca ggc acc gtg gcg 252 Ala Leu Phe Cys Gly Cys Gly His Val Ala Leu Ala Gly Thr Val Ala 50 55 60 att ctt gag caa cac ttc tcc acc aac gcc agt gac cat gcc ttg ctg 300 Ile Leu Glu Gln His Phe Ser Thr Asn Ala Ser Asp His Ala Leu Leu 65 70 75 80 agc gag gtg ata caa ctg atg cag tat gtc atc tat gga att gcg tcc 348 Ser Glu Val Ile Gln Leu Met Gln Tyr Val Ile Tyr Gly Ile Ala Ser 85 90 95 ttt ttc ttc ttg tat ggg atc att ctg ttg gca gaa ggc ttt tac acc 396 Phe Phe Phe Leu Tyr Gly Ile Ile Leu Leu Ala Glu Gly Phe Tyr Thr 100 105 110 aca agt gca gtg aaa gaa ctg cac ggt gag ttt aaa aca acc gct tgt 444 Thr Ser Ala Val Lys Glu Leu His Gly Glu Phe Lys Thr Thr Ala Cys 115 120 125 ggc cga tgc atc agt gga atg ttc gtt ttc ctc acc tat gtg ctt gga 492 Gly Arg Cys Ile Ser Gly Met Phe Val Phe Leu Thr Tyr Val Leu Gly 130 135 140 gtg gcc tgg ctg ggt gtg ttt ggt ttc tca gcg gtg ccc gtg ttt atg 540 Val Ala Trp Leu Gly Val Phe Gly Phe Ser Ala Val Pro Val Phe Met 145 150 155 160 ttc tac aac ata tgg tca act tgt gaa gtc atc aag tca ccg cag acc 588 Phe Tyr Asn Ile Trp Ser Thr Cys Glu Val Ile Lys Ser Pro Gln Thr 165 170 175 aac ggg acc acg ggt gtg gag cag atc tgt gtg gat atc cga caa tac 636 Asn Gly Thr Thr Gly Val Glu Gln Ile Cys Val Asp Ile Arg Gln Tyr 180 185 190 ggt atc att cct tgg aat gct ttc ccc gga aaa ata tgt ggc tct gcc 684 Gly Ile Ile Pro Trp Asn Ala Phe Pro Gly Lys Ile Cys Gly Ser Ala 195 200 205 ctg gag aac atc tgc aac aca aac gag ttc tac atg tcc tat cac ctg 732 Leu Glu Asn Ile Cys Asn Thr Asn Glu Phe Tyr Met Ser Tyr His Leu 210 215 220 ttc att gtg gcc tgt gca gga gct ggt gcc acc gtc att gcc ctg atc 780 Phe Ile Val Ala Cys Ala Gly Ala Gly Ala Thr Val Ile Ala Leu Ile 225 230 235 240 cac ttc ctc atg ata ctg tct tct aac tgg gct tac tta aag gat gcg 828 His Phe Leu Met Ile Leu Ser Ser Asn Trp Ala Tyr Leu Lys Asp Ala 245 250 255 agc aaa atg cag gct tac cag gat atc aaa gca aag gaa gaa cag gaa 876 Ser Lys Met Gln Ala Tyr Gln Asp Ile Lys Ala Lys Glu Glu Gln Glu 260 265 270 ctg caa gat atc cag tct cgg tca aaa gaa caa ctc aat tct tac aca 924 Leu Gln Asp Ile Gln Ser Arg Ser Lys Glu Gln Leu Asn Ser Tyr Thr 275 280 285 taaatgtttg ccagagtgtt tcggccgacg tatttacagc tctgacaaat catcagacag 984 ctgctctgca gtacagatgt gtatcccacc aaactaatgt agatgtacaa acacttcact 1044 gtctgtctca agctgctggg atgtatctct aggaaaacct tccagtgggt aaatcttttt 1104 ctttagaaca aatattggag gttcatgttg ccccatttaa agggcacact tttacaaatg 1164 atcgtcatac tttgggat 1182 48 288 PRT Homo sapiens 48 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 Gln Glu Arg Lys Gly Cys Phe Glu Cys Cys Ile Lys Cys Leu Gly Gly 20 25 30 Val Pro Tyr Ala Ser Leu Val Ala Thr Ile Leu Cys Phe Ser Gly Val 35 40 45 Ala Leu Phe Cys Gly Cys Gly His Val Ala Leu Ala Gly Thr Val Ala 50 55 60 Ile Leu Glu Gln His Phe Ser Thr Asn Ala Ser Asp His Ala Leu Leu 65 70 75 80 Ser Glu Val Ile Gln Leu Met Gln Tyr Val Ile Tyr Gly Ile Ala Ser 85 90 95 Phe Phe Phe Leu Tyr Gly Ile Ile Leu Leu Ala Glu Gly Phe Tyr Thr 100 105 110 Thr Ser Ala Val Lys Glu Leu His Gly Glu Phe Lys Thr Thr Ala Cys 115 120 125 Gly Arg Cys Ile Ser Gly Met Phe Val Phe Leu Thr Tyr Val Leu Gly 130 135 140 Val Ala Trp Leu Gly Val Phe Gly Phe Ser Ala Val Pro Val Phe Met 145 150 155 160 Phe Tyr Asn Ile Trp Ser Thr Cys Glu Val Ile Lys Ser Pro Gln Thr 165 170 175 Asn Gly Thr Thr Gly Val Glu Gln Ile Cys Val Asp Ile Arg Gln Tyr 180 185 190 Gly Ile Ile Pro Trp Asn Ala Phe Pro Gly Lys Ile Cys Gly Ser Ala 195 200 205 Leu Glu Asn Ile Cys Asn Thr Asn Glu Phe Tyr Met Ser Tyr His Leu 210 215 220 Phe Ile Val Ala Cys Ala Gly Ala Gly Ala Thr Val Ile Ala Leu Ile 225 230 235 240 His Phe Leu Met Ile Leu Ser Ser Asn Trp Ala Tyr Leu Lys Asp Ala 245 250 255 Ser Lys Met Gln Ala Tyr Gln Asp Ile Lys Ala Lys Glu Glu Gln Glu 260 265 270 Leu Gln Asp Ile Gln Ser Arg Ser Lys Glu Gln Leu Asn Ser Tyr Thr 275 280 285 49 1302 DNA Homo sapiens CDS (61)..(1044) 49 aggaggaaaa acaagtgtgt gttgggggga acagggggaa aagcattttt ggtggatggt 60 atg aag cca gcc atg gaa act gca gcc gag gaa aat act gaa caa agc 108 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 caa gag aga aaa gtg aac agc aga gct gaa atg gaa att ggc agg tac 156 Gln Glu Arg Lys Val Asn Ser Arg Ala Glu Met Glu Ile Gly Arg Tyr 20 25 30 cac tgg atg tac cca ggc tca aag aac cac cag tac cat ccc gtg cca 204 His Trp Met Tyr Pro Gly Ser Lys Asn His Gln Tyr His Pro Val Pro 35 40 45 acc ctg ggg gac agg gct agc ccc ttg agc agt cca ggc tgc ttt gaa 252 Thr Leu Gly Asp Arg Ala Ser Pro Leu Ser Ser Pro Gly Cys Phe Glu 50 55 60 tgc tgc atc aag tgt ctg gga gga gtc ccc tac gcc tcc ctg gtg gcc 300 Cys Cys Ile Lys Cys Leu Gly Gly Val Pro Tyr Ala Ser Leu Val Ala 65 70 75 80 acc atc ctc tgc ttc tcc ggg gtg gcc tta ttc tgc ggc tgt ggg cat 348 Thr Ile Leu Cys Phe Ser Gly Val Ala Leu Phe Cys Gly Cys Gly His 85 90 95 gtg gct ctc gca ggc acc gtg gcg att ctt gag caa cac ttc tcc acc 396 Val Ala Leu Ala Gly Thr Val Ala Ile Leu Glu Gln His Phe Ser Thr 100 105 110 aac gcc agt gac cat gcc ttg ctg agc gag gtg ata caa ctg atg cag 444 Asn Ala Ser Asp His Ala Leu Leu Ser Glu Val Ile Gln Leu Met Gln 115 120 125 tat gtc atc tat gga att gcg tcc ttt ttc ttc ttg tat ggg atc att 492 Tyr Val Ile Tyr Gly Ile Ala Ser Phe Phe Phe Leu Tyr Gly Ile Ile 130 135 140 ctg ttg gca gaa ggc ttt tac acc aca agt gca gtg aaa gaa ctg cac 540 Leu Leu Ala Glu Gly Phe Tyr Thr Thr Ser Ala Val Lys Glu Leu His 145 150 155 160 ggt gag ttt aaa aca acc gct tgt ggc cga tgc atc agt gga atg ttc 588 Gly Glu Phe Lys Thr Thr Ala Cys Gly Arg Cys Ile Ser Gly Met Phe 165 170 175 gtt ttc ctc acc tat gtg ctt gga gtg gcc tgg ctg ggt gtg ttt ggt 636 Val Phe Leu Thr Tyr Val Leu Gly Val Ala Trp Leu Gly Val Phe Gly 180 185 190 ttc tca gcg gtg ccc gtg ttt atg ttc tac aac ata tgg tca act tgt 684 Phe Ser Ala Val Pro Val Phe Met Phe Tyr Asn Ile Trp Ser Thr Cys 195 200 205 gaa gtc atc aag tca ccg cag acc aac ggg acc acg ggt gtg gag cag 732 Glu Val Ile Lys Ser Pro Gln Thr Asn Gly Thr Thr Gly Val Glu Gln 210 215 220 atc tgt gtg gat atc cga caa tac ggt atc att cct tgg aat gct ttc 780 Ile Cys Val Asp Ile Arg Gln Tyr Gly Ile Ile Pro Trp Asn Ala Phe 225 230 235 240 ccc gga aaa ata tgt ggc tct gcc ctg gag aac atc tgc aac aca aac 828 Pro Gly Lys Ile Cys Gly Ser Ala Leu Glu Asn Ile Cys Asn Thr Asn 245 250 255 gag ttc tac atg tcc tat cac ctg ttc att gtg gcc tgt gca gga gct 876 Glu Phe Tyr Met Ser Tyr His Leu Phe Ile Val Ala Cys Ala Gly Ala 260 265 270 ggt gcc acc gtc att gcc ctg atc cac ttc ctc atg ata ctg tct tct 924 Gly Ala Thr Val Ile Ala Leu Ile His Phe Leu Met Ile Leu Ser Ser 275 280 285 aac tgg gct tac tta aag gat gcg agc aaa atg cag gct tac cag gat 972 Asn Trp Ala Tyr Leu Lys Asp Ala Ser Lys Met Gln Ala Tyr Gln Asp 290 295 300 atc aaa gca aag gaa gaa cag gaa ctg caa gat atc cag tct cgg tca 1020 Ile Lys Ala Lys Glu Glu Gln Glu Leu Gln Asp Ile Gln Ser Arg Ser 305 310 315 320 aaa gaa caa ctc aat tct tac aca taaatgtttg ccagagtgtt tcggccgacg 1074 Lys Glu Gln Leu Asn Ser Tyr Thr 325 tatttacagc tctgacaaat catcagacag ctgctctgca gtacagatgt gtatcccacc 1134 aaactaatgt agatgtacaa acacttcact gtctgtctca agctgctggg atgtatctct 1194 aggaaaacct tccagtgggt aaatcttttt ctttagaaca aatattggag gttcatgttg 1254 ccccatttaa agggcacact tttacaaatg atcgtcatac tttgggat 1302 50 328 PRT Homo sapiens 50 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 Gln Glu Arg Lys Val Asn Ser Arg Ala Glu Met Glu Ile Gly Arg Tyr 20 25 30 His Trp Met Tyr Pro Gly Ser Lys Asn His Gln Tyr His Pro Val Pro 35 40 45 Thr Leu Gly Asp Arg Ala Ser Pro Leu Ser Ser Pro Gly Cys Phe Glu 50 55 60 Cys Cys Ile Lys Cys Leu Gly Gly Val Pro Tyr Ala Ser Leu Val Ala 65 70 75 80 Thr Ile Leu Cys Phe Ser Gly Val Ala Leu Phe Cys Gly Cys Gly His 85 90 95 Val Ala Leu Ala Gly Thr Val Ala Ile Leu Glu Gln His Phe Ser Thr 100 105 110 Asn Ala Ser Asp His Ala Leu Leu Ser Glu Val Ile Gln Leu Met Gln 115 120 125 Tyr Val Ile Tyr Gly Ile Ala Ser Phe Phe Phe Leu Tyr Gly Ile Ile 130 135 140 Leu Leu Ala Glu Gly Phe Tyr Thr Thr Ser Ala Val Lys Glu Leu His 145 150 155 160 Gly Glu Phe Lys Thr Thr Ala Cys Gly Arg Cys Ile Ser Gly Met Phe 165 170 175 Val Phe Leu Thr Tyr Val Leu Gly Val Ala Trp Leu Gly Val Phe Gly 180 185 190 Phe Ser Ala Val Pro Val Phe Met Phe Tyr Asn Ile Trp Ser Thr Cys 195 200 205 Glu Val Ile Lys Ser Pro Gln Thr Asn Gly Thr Thr Gly Val Glu Gln 210 215 220 Ile Cys Val Asp Ile Arg Gln Tyr Gly Ile Ile Pro Trp Asn Ala Phe 225 230 235 240 Pro Gly Lys Ile Cys Gly Ser Ala Leu Glu Asn Ile Cys Asn Thr Asn 245 250 255 Glu Phe Tyr Met Ser Tyr His Leu Phe Ile Val Ala Cys Ala Gly Ala 260 265 270 Gly Ala Thr Val Ile Ala Leu Ile His Phe Leu Met Ile Leu Ser Ser 275 280 285 Asn Trp Ala Tyr Leu Lys Asp Ala Ser Lys Met Gln Ala Tyr Gln Asp 290 295 300 Ile Lys Ala Lys Glu Glu Gln Glu Leu Gln Asp Ile Gln Ser Arg Ser 305 310 315 320 Lys Glu Gln Leu Asn Ser Tyr Thr 325 51 929 DNA Homo sapiens CDS (61)..(855) 51 aggaggaaaa acaagtgtgt gttgggggga acagggggaa aagcattttt ggtggatggt 60 atg aag cca gcc atg gaa act gca gcc gag gaa aat act gaa caa agc 108 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 caa gag aga aaa ggc tgc ttt gaa tgc tgc atc aag tgt ctg gga gga 156 Gln Glu Arg Lys Gly Cys Phe Glu Cys Cys Ile Lys Cys Leu Gly Gly 20 25 30 gtc ccc tac gcc tcc ctg gtg gcc acc atc ctc tgc ttc tcc ggg gtg 204 Val Pro Tyr Ala Ser Leu Val Ala Thr Ile Leu Cys Phe Ser Gly Val 35 40 45 gcc tta ttc tgc ggc tgt ggg cat gtg gct ctc gca ggc acc gtg gcg 252 Ala Leu Phe Cys Gly Cys Gly His Val Ala Leu Ala Gly Thr Val Ala 50 55 60 att ctt gag caa cac ttc tcc acc aac gcc agt gac cat gcc ttg ctg 300 Ile Leu Glu Gln His Phe Ser Thr Asn Ala Ser Asp His Ala Leu Leu 65 70 75 80 agc gag gtg ata caa ctg atg cag tat gtc atc tat gga att gcg tcc 348 Ser Glu Val Ile Gln Leu Met Gln Tyr Val Ile Tyr Gly Ile Ala Ser 85 90 95 ttt ttc ttc ttg tat ggg atc att ctg ttg gca gaa ggc ttt tac acc 396 Phe Phe Phe Leu Tyr Gly Ile Ile Leu Leu Ala Glu Gly Phe Tyr Thr 100 105 110 aca agt gca gtg aaa gaa ctg cac ggt gag ttt aaa aca acc gct tgt 444 Thr Ser Ala Val Lys Glu Leu His Gly Glu Phe Lys Thr Thr Ala Cys 115 120 125 ggc cga tgc atc agt gga atg ttc gtt ttc ctc acc tat gtg ctt gga 492 Gly Arg Cys Ile Ser Gly Met Phe Val Phe Leu Thr Tyr Val Leu Gly 130 135 140 gtg gcc tgg ctg ggt gtg ttt ggt ttc tca gcg gtg ccc gtg ttt atg 540 Val Ala Trp Leu Gly Val Phe Gly Phe Ser Ala Val Pro Val Phe Met 145 150 155 160 ttc tac aac ata tgg tca act tgt gaa gtc atc aag tca ccg cag acc 588 Phe Tyr Asn Ile Trp Ser Thr Cys Glu Val Ile Lys Ser Pro Gln Thr 165 170 175 aac ggg acc acg ggt gtg gag cag atc tgt gtg gat atc cga caa tac 636 Asn Gly Thr Thr Gly Val Glu Gln Ile Cys Val Asp Ile Arg Gln Tyr 180 185 190 ggt atc att cct tgg aat gct ttc ccc gga aaa ata tgt ggc tct gcc 684 Gly Ile Ile Pro Trp Asn Ala Phe Pro Gly Lys Ile Cys Gly Ser Ala 195 200 205 ctg gag aac atc tgc aac aca aac gag ttc tac atg tcc tat cac ctg 732 Leu Glu Asn Ile Cys Asn Thr Asn Glu Phe Tyr Met Ser Tyr His Leu 210 215 220 ttc att gtg gcc tgt gca gga gct ggt gcc acc gtc att gcc ctg ctg 780 Phe Ile Val Ala Cys Ala Gly Ala Gly Ala Thr Val Ile Ala Leu Leu 225 230 235 240 atc tac atg atg gct act aca tat aac tat gcg gtt ttg aag ttt aag 828 Ile Tyr Met Met Ala Thr Thr Tyr Asn Tyr Ala Val Leu Lys Phe Lys 245 250 255 agt cgg gaa gat tgc tgc act aaa ttc taaattgcat aaggagtttt 875 Ser Arg Glu Asp Cys Cys Thr Lys Phe 260 265 agagagctat gctctgtagc atgaaatatc actgacactc cagaaagggc gatt 929 52 265 PRT Homo sapiens 52 Met Lys Pro Ala Met Glu Thr Ala Ala Glu Glu Asn Thr Glu Gln Ser 1 5 10 15 Gln Glu Arg Lys Gly Cys Phe Glu Cys Cys Ile Lys Cys Leu Gly Gly 20 25 30 Val Pro Tyr Ala Ser Leu Val Ala Thr Ile Leu Cys Phe Ser Gly Val 35 40 45 Ala Leu Phe Cys Gly Cys Gly His Val Ala Leu Ala Gly Thr Val Ala 50 55 60 Ile Leu Glu Gln His Phe Ser Thr Asn Ala Ser Asp His Ala Leu Leu 65 70 75 80 Ser Glu Val Ile Gln Leu Met Gln Tyr Val Ile Tyr Gly Ile Ala Ser 85 90 95 Phe Phe Phe Leu Tyr Gly Ile Ile Leu Leu Ala Glu Gly Phe Tyr Thr 100 105 110 Thr Ser Ala Val Lys Glu Leu His Gly Glu Phe Lys Thr Thr Ala Cys 115 120 125 Gly Arg Cys Ile Ser Gly Met Phe Val Phe Leu Thr Tyr Val Leu Gly 130 135 140 Val Ala Trp Leu Gly Val Phe Gly Phe Ser Ala Val Pro Val Phe Met 145 150 155 160 Phe Tyr Asn Ile Trp Ser Thr Cys Glu Val Ile Lys Ser Pro Gln Thr 165 170 175 Asn Gly Thr Thr Gly Val Glu Gln Ile Cys Val Asp Ile Arg Gln Tyr 180 185 190 Gly Ile Ile Pro Trp Asn Ala Phe Pro Gly Lys Ile Cys Gly Ser Ala 195 200 205 Leu Glu Asn Ile Cys Asn Thr Asn Glu Phe Tyr Met Ser Tyr His Leu 210 215 220 Phe Ile Val Ala Cys Ala Gly Ala Gly Ala Thr Val Ile Ala Leu Leu 225 230 235 240 Ile Tyr Met Met Ala Thr Thr Tyr Asn Tyr Ala Val Leu Lys Phe Lys 245 250 255 Ser Arg Glu Asp Cys Cys Thr Lys Phe 260 265 53 1201 DNA Homo sapiens CDS (24)..(1118) 53 tttgatctga agactagggg aca atg gat atc ata gag aca gca aaa ctt gaa 53 Met Asp Ile Ile Glu Thr Ala Lys Leu Glu 1 5 10 gaa cat ttg gaa aat caa ccc agt gat cct acg aac act tat gca aga 101 Glu His Leu Glu Asn Gln Pro Ser Asp Pro Thr Asn Thr Tyr Ala Arg 15 20 25 ccc gct gaa cct gtt gaa gaa gaa aac aaa aat ggc aat ggt aaa ccc 149 Pro Ala Glu Pro Val Glu Glu Glu Asn Lys Asn Gly Asn Gly Lys Pro 30 35 40 aag agc tta tcc agt ggg ctg cga aaa ggc acc aaa aag tac ccg gac 197 Lys Ser Leu Ser Ser Gly Leu Arg Lys Gly Thr Lys Lys Tyr Pro Asp 45 50 55 tat atc caa att gct atg ccc act gaa tca agg aac aaa ttt cca cta 245 Tyr Ile Gln Ile Ala Met Pro Thr Glu Ser Arg Asn Lys Phe Pro Leu 60 65 70 gag tgg tgg aaa acg ggc att gcc ttc ata tat gca gtt ttc aac ctc 293 Glu Trp Trp Lys Thr Gly Ile Ala Phe Ile Tyr Ala Val Phe Asn Leu 75 80 85 90 gtc ttg aca acc gtc atg atc aca gtt gta cat gag agg gtc cct ccc 341 Val Leu Thr Thr Val Met Ile Thr Val Val His Glu Arg Val Pro Pro 95 100 105 aag gag ctt agc cct cca ctc cca gac aag ttt ttt gat tac att gat 389 Lys Glu Leu Ser Pro Pro Leu Pro Asp Lys Phe Phe Asp Tyr Ile Asp 110 115 120 agg gtg aaa tgg gca ttt tct gta tca gaa ata aat ggg att ata tta 437 Arg Val Lys Trp Ala Phe Ser Val Ser Glu Ile Asn Gly Ile Ile Leu 125 130 135 gtt gga tta tgg atc acc cag tgg ctg ttt ctg aga tac aag tca ata 485 Val Gly Leu Trp Ile Thr Gln Trp Leu Phe Leu Arg Tyr Lys Ser Ile 140 145 150 gtg gga cgc aga ttc tgt ttt att att gga act tta tac ctg tat cgc 533 Val Gly Arg Arg Phe Cys Phe Ile Ile Gly Thr Leu Tyr Leu Tyr Arg 155 160 165 170 tgc att aca atg tat gtt act act cta cct gtg cct gga atg cat ttc 581 Cys Ile Thr Met Tyr Val Thr Thr Leu Pro Val Pro Gly Met His Phe 175 180 185 cag tgt gct cca aag ctc aat gga gac tct cag gca aaa gtt caa cgg 629 Gln Cys Ala Pro Lys Leu Asn Gly Asp Ser Gln Ala Lys Val Gln Arg 190 195 200 att cta cga ttg att tct ggt ggt gga ttg tcc ata act gga tca cat 677 Ile Leu Arg Leu Ile Ser Gly Gly Gly Leu Ser Ile Thr Gly Ser His 205 210 215 atc tta tgt gga gac ttc ctc ttc agc ggt cac acg gtt acg ctg aca 725 Ile Leu Cys Gly Asp Phe Leu Phe Ser Gly His Thr Val Thr Leu Thr 220 225 230 ctg act tat ttg ttc atc aaa gaa tat tcg cct cgt cac ttc tgg tgg 773 Leu Thr Tyr Leu Phe Ile Lys Glu Tyr Ser Pro Arg His Phe Trp Trp 235 240 245 250 tat cat tta atc tgc tgg ctg ctg agt gct gcc ggg atc atc tgc att 821 Tyr His Leu Ile Cys Trp Leu Leu Ser Ala Ala Gly Ile Ile Cys Ile 255 260 265 ctt gta gca cac gaa cac tac act atc gat gtg atc att gct tat tat 869 Leu Val Ala His Glu His Tyr Thr Ile Asp Val Ile Ile Ala Tyr Tyr 270 275 280 atc aca aca cga ctg ttt tgg tgg tac cat tca atg gcc aat gaa aag 917 Ile Thr Thr Arg Leu Phe Trp Trp Tyr His Ser Met Ala Asn Glu Lys 285 290 295 aac ttg aag gtc tct tca cag act aat ttc tta tct cga gca tgg tgg 965 Asn Leu Lys Val Ser Ser Gln Thr Asn Phe Leu Ser Arg Ala Trp Trp 300 305 310 ttc ccc atc ttt tat ttt ttt gag aaa aat gta caa ggc tca att cct 1013 Phe Pro Ile Phe Tyr Phe Phe Glu Lys Asn Val Gln Gly Ser Ile Pro 315 320 325 330 tgc tgc ttc tcc tgg ccg ctg tct tgg cct cct ggc tgc ttc aaa tca 1061 Cys Cys Phe Ser Trp Pro Leu Ser Trp Pro Pro Gly Cys Phe Lys Ser 335 340 345 tca tgc aaa aag tat tca cgg gtt cag aag att ggt gaa gac aat gag 1109 Ser Cys Lys Lys Tyr Ser Arg Val Gln Lys Ile Gly Glu Asp Asn Glu 350 355 360 aaa tcg acc tgaggagcaa aacaaaggca tcagctctta caccaaaaga 1158 Lys Ser Thr 365 gttaacgctg taaccaaaga agggcgattc cagcacactg cgc 1201 54 365 PRT Homo sapiens 54 Met Asp Ile Ile Glu Thr Ala Lys Leu Glu Glu His Leu Glu Asn Gln 1 5 10 15 Pro Ser Asp Pro Thr Asn Thr Tyr Ala Arg Pro Ala Glu Pro Val Glu 20 25 30 Glu Glu Asn Lys Asn Gly Asn Gly Lys Pro Lys Ser Leu Ser Ser Gly 35 40 45 Leu Arg Lys Gly Thr Lys Lys Tyr Pro Asp Tyr Ile Gln Ile Ala Met 50 55 60 Pro Thr Glu Ser Arg Asn Lys Phe Pro Leu Glu Trp Trp Lys Thr Gly 65 70 75 80 Ile Ala Phe Ile Tyr Ala Val Phe Asn Leu Val Leu Thr Thr Val Met 85 90 95 Ile Thr Val Val His Glu Arg Val Pro Pro Lys Glu Leu Ser Pro Pro 100 105 110 Leu Pro Asp Lys Phe Phe Asp Tyr Ile Asp Arg Val Lys Trp Ala Phe 115 120 125 Ser Val Ser Glu Ile Asn Gly Ile Ile Leu Val Gly Leu Trp Ile Thr 130 135 140 Gln Trp Leu Phe Leu Arg Tyr Lys Ser Ile Val Gly Arg Arg Phe Cys 145 150 155 160 Phe Ile Ile Gly Thr Leu Tyr Leu Tyr Arg Cys Ile Thr Met Tyr Val 165 170 175 Thr Thr Leu Pro Val Pro Gly Met His Phe Gln Cys Ala Pro Lys Leu 180 185 190 Asn Gly Asp Ser Gln Ala Lys Val Gln Arg Ile Leu Arg Leu Ile Ser 195 200 205 Gly Gly Gly Leu Ser Ile Thr Gly Ser His Ile Leu Cys Gly Asp Phe 210 215 220 Leu Phe Ser Gly His Thr Val Thr Leu Thr Leu Thr Tyr Leu Phe Ile 225 230 235 240 Lys Glu Tyr Ser Pro Arg His Phe Trp Trp Tyr His Leu Ile Cys Trp 245 250 255 Leu Leu Ser Ala Ala Gly Ile Ile Cys Ile Leu Val Ala His Glu His 260 265 270 Tyr Thr Ile Asp Val Ile Ile Ala Tyr Tyr Ile Thr Thr Arg Leu Phe 275 280 285 Trp Trp Tyr His Ser Met Ala Asn Glu Lys Asn Leu Lys Val Ser Ser 290 295 300 Gln Thr Asn Phe Leu Ser Arg Ala Trp Trp Phe Pro Ile Phe Tyr Phe 305 310 315 320 Phe Glu Lys Asn Val Gln Gly Ser Ile Pro Cys Cys Phe Ser Trp Pro 325 330 335 Leu Ser Trp Pro Pro Gly Cys Phe Lys Ser Ser Cys Lys Lys Tyr Ser 340 345 350 Arg Val Gln Lys Ile Gly Glu Asp Asn Glu Lys Ser Thr 355 360 365 55 1893 DNA Homo sapiens CDS (463)..(1488) 55 cggagctacc ttataaagac catctgtaca tccactgtga aatggagttt caaaatcaca 60 agcttctttc ccacatgaac ataagactag gagcacatat ggaagagtaa agttgaaggg 120 aatttggatg atgatttggc aagatgctgt gggatagtaa catctttttg agggaagaat 180 tggcttcctt tcttgaaagt ggtgaaggta cagcatatag ctgcatggaa gaaacagtaa 240 tcggatggct accttctaca ttttgtatta ggaaacaaag tccattgtaa gagtccatgt 300 tgatcttgga aatagaagga ttgaaaaaag ctaaatttcc acaaagaaca agaacttgac 360 catctccttt ttgatctgaa gactagggga caatggatat catagagaca gcaaaacttg 420 aagaacattt ggaaaatcaa cccagtgatc ctacgaacac tt atg caa gac ccg 474 Met Gln Asp Pro 1 ctg aac ctg ttg aag aag aaa aca aaa atg gca att ggt aaa ccc aag 522 Leu Asn Leu Leu Lys Lys Lys Thr Lys Met Ala Ile Gly Lys Pro Lys 5 10 15 20 agc tta tcc agt ggg ctg cga aaa ggc acc aaa aag tac ccg gac tat 570 Ser Leu Ser Ser Gly Leu Arg Lys Gly Thr Lys Lys Tyr Pro Asp Tyr 25 30 35 atc caa att gct atg ccc act gaa tca agg aac aaa ttt cca cta gag 618 Ile Gln Ile Ala Met Pro Thr Glu Ser Arg Asn Lys Phe Pro Leu Glu 40 45 50 tgg tgg aaa acg ggc att gcc ttc ata tat gca gtt ttc aac ctc gtc 666 Trp Trp Lys Thr Gly Ile Ala Phe Ile Tyr Ala Val Phe Asn Leu Val 55 60 65 ttg aca acc gtc atg atc aca gtt gta cat gag agg gtc cct ccc aag 714 Leu Thr Thr Val Met Ile Thr Val Val His Glu Arg Val Pro Pro Lys 70 75 80 gag ctt agc cct cca ctc cca gac aag ttt ttt gat tac att gat agg 762 Glu Leu Ser Pro Pro Leu Pro Asp Lys Phe Phe Asp Tyr Ile Asp Arg 85 90 95 100 gtg aaa tgg gca ttt tct gta tca gaa ata aat ggg att ata tta gtt 810 Val Lys Trp Ala Phe Ser Val Ser Glu Ile Asn Gly Ile Ile Leu Val 105 110 115 gga tta tgg atc acc cag tgg ctg ttt ctg aga tac aag tca ata gtg 858 Gly Leu Trp Ile Thr Gln Trp Leu Phe Leu Arg Tyr Lys Ser Ile Val 120 125 130 gga cgc aga ttc tgt ttt att att gga act tta tac ctg tat cgc tgc 906 Gly Arg Arg Phe Cys Phe Ile Ile Gly Thr Leu Tyr Leu Tyr Arg Cys 135 140 145 att aca atg tat gtt act act cta cct gtg cct gga atg cat ttc cag 954 Ile Thr Met Tyr Val Thr Thr Leu Pro Val Pro Gly Met His Phe Gln 150 155 160 tgt gct cca aag ctc aat gga gac tct cag gca aaa gtt caa cgg att 1002 Cys Ala Pro Lys Leu Asn Gly Asp Ser Gln Ala Lys Val Gln Arg Ile 165 170 175 180 cta cga ttg att tct ggt ggt gga ttg tcc ata act gga tca cat atc 1050 Leu Arg Leu Ile Ser Gly Gly Gly Leu Ser Ile Thr Gly Ser His Ile 185 190 195 tta tgt gga gac ttc ctc ttc agc ggt cac acg gtt acg ctg aca ctg 1098 Leu Cys Gly Asp Phe Leu Phe Ser Gly His Thr Val Thr Leu Thr Leu 200 205 210 act tat ttg ttc atc aaa gaa gat tcg cct cgt cac ttc tgg tgg tat 1146 Thr Tyr Leu Phe Ile Lys Glu Asp Ser Pro Arg His Phe Trp Trp Tyr 215 220 225 cat tta atc tgc tgg ctg ctg agt gct gcc ggg atc atc tgc att ctt 1194 His Leu Ile Cys Trp Leu Leu Ser Ala Ala Gly Ile Ile Cys Ile Leu 230 235 240 gta gca cac gaa cac tac act atc gat gtg atc att gct tat tat atc 1242 Val Ala His Glu His Tyr Thr Ile Asp Val Ile Ile Ala Tyr Tyr Ile 245 250 255 260 aca aca cga ctg ttt tgg tgg tac cat tca atg gcc aat gaa aag aac 1290 Thr Thr Arg Leu Phe Trp Trp Tyr His Ser Met Ala Asn Glu Lys Asn 265 270 275 ttg aag gtc tct tca cag act aat ttc tta tct cga gca tgg tgg ttc 1338 Leu Lys Val Ser Ser Gln Thr Asn Phe Leu Ser Arg Ala Trp Trp Phe 280 285 290 ccc atc ttt tat ttt ttt gag aaa aat gta caa ggc tca att cct tgc 1386 Pro Ile Phe Tyr Phe Phe Glu Lys Asn Val Gln Gly Ser Ile Pro Cys 295 300 305 tgc ttc tcc tgg ccg ctg tct tgg cct cct ggc tgc ttc aaa tca tca 1434 Cys Phe Ser Trp Pro Leu Ser Trp Pro Pro Gly Cys Phe Lys Ser Ser 310 315 320 tgc aaa aag tat tca cgg gtt cag aag att ggt gaa gac aat gag aaa 1482 Cys Lys Lys Tyr Ser Arg Val Gln Lys Ile Gly Glu Asp Asn Glu Lys 325 330 335 340 tcg acc tgaggagcaa aacaaaggca tcagctctta caccaaaaga gttaacgctg 1538 Ser Thr taaccaaagg tatagttttg ttttttattt taggagaact gactggtaaa tgaagaaatg 1598 gaccaaattt tgtgtaaacg attagaaaga tgaacaaagt attgcccttt gactggtttt 1658 cttcttcatc ctgagaaaga tacattctct tgcagctctt cattcattgg tgacaagccc 1718 ccaccccggg actttactaa tgagcttgtt aaagaggtgc caaagaacat attcctcctt 1778 tctttattct ttctccacca aaaccctcta cttcagaatt ttttcaggat atttttcagc 1838 ccaaggtcag aagaatgtgt taatatttta aataaaatat ctggacatct acaaa 1893 56 342 PRT Homo sapiens 56 Met Gln Asp Pro Leu Asn Leu Leu Lys Lys Lys Thr Lys Met Ala Ile 1 5 10 15 Gly Lys Pro Lys Ser Leu Ser Ser Gly Leu Arg Lys Gly Thr Lys Lys 20 25 30 Tyr Pro Asp Tyr Ile Gln Ile Ala Met Pro Thr Glu Ser Arg Asn Lys 35 40 45 Phe Pro Leu Glu Trp Trp Lys Thr Gly Ile Ala Phe Ile Tyr Ala Val 50 55 60 Phe Asn Leu Val Leu Thr Thr Val Met Ile Thr Val Val His Glu Arg 65 70 75 80 Val Pro Pro Lys Glu Leu Ser Pro Pro Leu Pro Asp Lys Phe Phe Asp 85 90 95 Tyr Ile Asp Arg Val Lys Trp Ala Phe Ser Val Ser Glu Ile Asn Gly 100 105 110 Ile Ile Leu Val Gly Leu Trp Ile Thr Gln Trp Leu Phe Leu Arg Tyr 115 120 125 Lys Ser Ile Val Gly Arg Arg Phe Cys Phe Ile Ile Gly Thr Leu Tyr 130 135 140 Leu Tyr Arg Cys Ile Thr Met Tyr Val Thr Thr Leu Pro Val Pro Gly 145 150 155 160 Met His Phe Gln Cys Ala Pro Lys Leu Asn Gly Asp Ser Gln Ala Lys 165 170 175 Val Gln Arg Ile Leu Arg Leu Ile Ser Gly Gly Gly Leu Ser Ile Thr 180 185 190 Gly Ser His Ile Leu Cys Gly Asp Phe Leu Phe Ser Gly His Thr Val 195 200 205 Thr Leu Thr Leu Thr Tyr Leu Phe Ile Lys Glu Asp Ser Pro Arg His 210 215 220 Phe Trp Trp Tyr His Leu Ile Cys Trp Leu Leu Ser Ala Ala Gly Ile 225 230 235 240 Ile Cys Ile Leu Val Ala His Glu His Tyr Thr Ile Asp Val Ile Ile 245 250 255 Ala Tyr Tyr Ile Thr Thr Arg Leu Phe Trp Trp Tyr His Ser Met Ala 260 265 270 Asn Glu Lys Asn Leu Lys Val Ser Ser Gln Thr Asn Phe Leu Ser Arg 275 280 285 Ala Trp Trp Phe Pro Ile Phe Tyr Phe Phe Glu Lys Asn Val Gln Gly 290 295 300 Ser Ile Pro Cys Cys Phe Ser Trp Pro Leu Ser Trp Pro Pro Gly Cys 305 310 315 320 Phe Lys Ser Ser Cys Lys Lys Tyr Ser Arg Val Gln Lys Ile Gly Glu 325 330 335 Asp Asn Glu Lys Ser Thr 340 57 1785 DNA Homo sapiens CDS (394)..(1110) 57 gtcgccagct gaggcggttt gtaagttttg ggtcgcagta tgctagaatt ttgaggctcc 60 cttctgatga aaattgagct gtccatgcag ccatggaacc cgggttacag cagtgagggg 120 gccacggctc aagaaactta cacatgtcca aaaatgattg agatggagca ggcggaggcc 180 cagcttgctg agttagacct gctagccagt atgttccctg gtgagaatga gctcatagtg 240 aatgaccagc tggctgtagc agaactgaaa gattgtattg aaaagaagac aatggagggg 300 cgatcttcaa aagtctactt tactatcaat atgaacctgg atgtatctga cgaaaaaatg 360 gtaattcagt tttgctttta gagggattga aac atg ttg aga ctt aaa aca ttg 414 Met Leu Arg Leu Lys Thr Leu 1 5 gtt agt gca ctt ttt ctt ctt ctc ttt aat cag gcg atg ttt tct ctg 462 Val Ser Ala Leu Phe Leu Leu Leu Phe Asn Gln Ala Met Phe Ser Leu 10 15 20 gcc tgt att ctt ccc ttt aaa tac ccg gca gtt ctg cct gaa att act 510 Ala Cys Ile Leu Pro Phe Lys Tyr Pro Ala Val Leu Pro Glu Ile Thr 25 30 35 gtc aga tca gta tta ttg agt aga tcc cag cag act cag ctg aac aca 558 Val Arg Ser Val Leu Leu Ser Arg Ser Gln Gln Thr Gln Leu Asn Thr 40 45 50 55 gat ctg act gca ttc ctg caa aaa cat tgt cat gga gat gtt tgt ata 606 Asp Leu Thr Ala Phe Leu Gln Lys His Cys His Gly Asp Val Cys Ile 60 65 70 ctg aat gcc aca gag tgg gtt aga gaa cac gcc tct ggc tat gtc agc 654 Leu Asn Ala Thr Glu Trp Val Arg Glu His Ala Ser Gly Tyr Val Ser 75 80 85 aga gat act tca tct tca ccc acc aca gga agc aca gtc cag tca gtt 702 Arg Asp Thr Ser Ser Ser Pro Thr Thr Gly Ser Thr Val Gln Ser Val 90 95 100 gac ctc atc ttc acg aga ctc tgg atc tac agc cat cat atc tat aac 750 Asp Leu Ile Phe Thr Arg Leu Trp Ile Tyr Ser His His Ile Tyr Asn 105 110 115 aaa tgc aaa aga aag aat att cta gag tgg gca aag gag ctt tcc ctg 798 Lys Cys Lys Arg Lys Asn Ile Leu Glu Trp Ala Lys Glu Leu Ser Leu 120 125 130 135 tct ggg ttt agc atg cct gga aaa cct ggt gtt gtt tgt gtg gaa ggc 846 Ser Gly Phe Ser Met Pro Gly Lys Pro Gly Val Val Cys Val Glu Gly 140 145 150 cca caa agt gcc tgt gaa gaa ttc tgg tca aga ctc aga aaa tta aac 894 Pro Gln Ser Ala Cys Glu Glu Phe Trp Ser Arg Leu Arg Lys Leu Asn 155 160 165 tgg aag aga att tta att cgc cat cga gaa gac att cct ttt gat ggt 942 Trp Lys Arg Ile Leu Ile Arg His Arg Glu Asp Ile Pro Phe Asp Gly 170 175 180 aca aat gat gaa acg gaa aga caa agg aaa ttt tcc att ttt gaa gaa 990 Thr Asn Asp Glu Thr Glu Arg Gln Arg Lys Phe Ser Ile Phe Glu Glu 185 190 195 aaa gtg ttc agt gtt aat gga gcc agg gga aac cac atg gac ttt ggt 1038 Lys Val Phe Ser Val Asn Gly Ala Arg Gly Asn His Met Asp Phe Gly 200 205 210 215 cag ctc tat cag ttc tta aac acc aaa gga tgt ggg gat gtt ttc cag 1086 Gln Leu Tyr Gln Phe Leu Asn Thr Lys Gly Cys Gly Asp Val Phe Gln 220 225 230 atg ttc ttt ggt gta gaa gga caa tgacatcaag agtagttgaa agtatcttgc 1140 Met Phe Phe Gly Val Glu Gly Gln 235 cactgttggc cttttgattt ttttttccca ctttttcttg aaagattaag taattttatt 1200 ttagttccat tctagaatgt tggggagtgg ggcacaagaa aaaatagtat agctgaaatg 1260 catctgttaa aaatgtcatg attgaaagca gaactgagtt tcaaattaca accttaaaat 1320 tgttgttaga tatttcttca catatcagct gcccattttg aaaaagaaat tatccataaa 1380 ggtaatgttg gtgctccaat ttgccagcca ttcccaaccc ccttctccct tacctgcctt 1440 cactaaagaa cccagaaaag ctaattgctc ccctttcagc ctctgttgca actaacaact 1500 ctcagtggcc tcaggacaca gctttggcct tgggaattct gggaaaactt ttacttcctg 1560 attaaagata catatgcagc taggccacct cctccccccc ttactgccat aaacaccaaa 1620 gtgatgactg gagctggagg agttatttga accacgacgg aagggccaag agaaccacga 1680 agatgccagt tgccacattg ttgagctgct gacccaacac cagccattgc ctgtctctaa 1740 acatcttatg aaataaaacc aattttgttt aaaaaaaaaa aaaaa 1785 58 239 PRT Homo sapiens 58 Met Leu Arg Leu Lys Thr Leu Val Ser Ala Leu Phe Leu Leu Leu Phe 1 5 10 15 Asn Gln Ala Met Phe Ser Leu Ala Cys Ile Leu Pro Phe Lys Tyr Pro 20 25 30 Ala Val Leu Pro Glu Ile Thr Val Arg Ser Val Leu Leu Ser Arg Ser 35 40 45 Gln Gln Thr Gln Leu Asn Thr Asp Leu Thr Ala Phe Leu Gln Lys His 50 55 60 Cys His Gly Asp Val Cys Ile Leu Asn Ala Thr Glu Trp Val Arg Glu 65 70 75 80 His Ala Ser Gly Tyr Val Ser Arg Asp Thr Ser Ser Ser Pro Thr Thr 85 90 95 Gly Ser Thr Val Gln Ser Val Asp Leu Ile Phe Thr Arg Leu Trp Ile 100 105 110 Tyr Ser His His Ile Tyr Asn Lys Cys Lys Arg Lys Asn Ile Leu Glu 115 120 125 Trp Ala Lys Glu Leu Ser Leu Ser Gly Phe Ser Met Pro Gly Lys Pro 130 135 140 Gly Val Val Cys Val Glu Gly Pro Gln Ser Ala Cys Glu Glu Phe Trp 145 150 155 160 Ser Arg Leu Arg Lys Leu Asn Trp Lys Arg Ile Leu Ile Arg His Arg 165 170 175 Glu Asp Ile Pro Phe Asp Gly Thr Asn Asp Glu Thr Glu Arg Gln Arg 180 185 190 Lys Phe Ser Ile Phe Glu Glu Lys Val Phe Ser Val Asn Gly Ala Arg 195 200 205 Gly Asn His Met Asp Phe Gly Gln Leu Tyr Gln Phe Leu Asn Thr Lys 210 215 220 Gly Cys Gly Asp Val Phe Gln Met Phe Phe Gly Val Glu Gly Gln 225 230 235 59 1776 DNA Homo sapiens CDS (14)..(1750) 59 caccggatcc acc atg tcc gcg ctg cga cct ctc ctg ctt ctg ctg ctg 49 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu 1 5 10 cct ctg tgt ccc ggt cct ggt ccc gga ccc ggg agc gag gca aag gtc 97 Pro Leu Cys Pro Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val 15 20 25 acc cgg agt tgt gca gag acc cgg cag gtg ctg ggg gcc cgg gga tat 145 Thr Arg Ser Cys Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr 30 35 40 agc tta aac cta atc cct ccc gcc ctg atc tca ggt gag cac ctc cgg 193 Ser Leu Asn Leu Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg 45 50 55 60 gtc tgt ccc cag gag tac acc tgc tgt tcc agt gag aca gag cag agg 241 Val Cys Pro Gln Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg 65 70 75 ctg atc agg gag act gag gcc acc ttc cga ggc ctg gtg gag gac agc 289 Leu Ile Arg Glu Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser 80 85 90 ggc tcc ttt ctg gtt cac aca ctg gct gcc agg cac aga aaa ttt gat 337 Gly Ser Phe Leu Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp 95 100 105 gag ttt ttt ctg gag atg ctc tca gta gcc cag cac tct ctg acc cag 385 Glu Phe Phe Leu Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln 110 115 120 ctc ttc tcc cac tcc tac ggc cgc ctg tat gcc cag cac gcc ctc ata 433 Leu Phe Ser His Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile 125 130 135 140 ttc aat ggc ctg ttc tct cgg ctg cga gac ttc tat ggg gaa tct ggt 481 Phe Asn Gly Leu Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly 145 150 155 gag ggg ttg gat gac acc ctg gcg gat ttc tgg gca cag ctc ctg gag 529 Glu Gly Leu Asp Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu 160 165 170 aga gtg ttc ccg ctg ctg cac cca cag tac agc ttc ccc cct gac tac 577 Arg Val Phe Pro Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr 175 180 185 ctg ctc tgc ctc tca cgc ttg gcc tca tct acc gat ggc tct ctg cag 625 Leu Leu Cys Leu Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln 190 195 200 ccc ttt ggg gac tca ccc cgc cgc ctc cgc ctg cag ata acc cgg acc 673 Pro Phe Gly Asp Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr 205 210 215 220 ctg gtg gct gcc cga gcc ttt gtg cag ggc ctg gag act gga aga aat 721 Leu Val Ala Ala Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn 225 230 235 gtg gtc agc gaa gcg ctt aag gtg ccg gtg tct gaa ggc tgc agc cag 769 Val Val Ser Glu Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln 240 245 250 gct ctg atg cgt ctc atc ggc tgt ccc ctg tgc cgg ggg gtc ccc tca 817 Ala Leu Met Arg Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser 255 260 265 ctt atg ccc tgc cag ggc ttc tgc ctc aac gtg gtt cgt ggc tgt ctc 865 Leu Met Pro Cys Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu 270 275 280 agc agc agg gga ctg gag cct gac tgg ggc aac tat ctg gat ggt ctc 913 Ser Ser Arg Gly Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu 285 290 295 300 ctg atc ctg gct gat aag ctc cag ggc ccc ttt tcc ttt gag ctg acg 961 Leu Ile Leu Ala Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr 305 310 315 gcc gag tcc att ggg gtg aag atc tcg gag ggt ttg atg tac ctg cag 1009 Ala Glu Ser Ile Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln 320 325 330 gaa aac agt gcg aag gtg tcc gcc cag gtg ttt cag gag tgc ggc ccc 1057 Glu Asn Ser Ala Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro 335 340 345 ccc gac ccg gtg cct gcc cgc aac cgt cga gcc ccg ccg ccc cgg gaa 1105 Pro Asp Pro Val Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu 350 355 360 gag gcg ggc cgg ctg tgg tcg atg gtg acc gag gag gag cgg ccc acg 1153 Glu Ala Gly Arg Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr 365 370 375 380 acg gcc gca ggc acc aac ctg cac cgg ctg gtg tgg gag ctc cgc gag 1201 Thr Ala Ala Gly Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu 385 390 395 cgt ctg gcc cgg atg cgg ggc ttc tgg gcc cgg ctg tcc ctg acg gtg 1249 Arg Leu Ala Arg Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val 400 405 410 tgc gga gac tct cgc atg gca gcg gac gcc tcg ctg gag gcg gcg ccc 1297 Cys Gly Asp Ser Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro 415 420 425 tgc tgg acc gga gcc ggg cgg ggc cgg tac ttg ccg cca gtg gtc ggg 1345 Cys Trp Thr Gly Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly 430 435 440 ggc tcc ccg gcc gag cag gtc aac aac ccc gag ctc aag gtg gac gcc 1393 Gly Ser Pro Ala Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala 445 450 455 460 tcg ggc ccc gat gtc ccg aca cgg cgg cgt cga cta cag ctc cgg gcg 1441 Ser Gly Pro Asp Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala 465 470 475 gcc acg gcc aga atg aaa acg gcc gca ctg gga cac gac ctg gac ggg 1489 Ala Thr Ala Arg Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly 480 485 490 cag gac gcg gat gag gat gcc agc ggc tct gga ggg gga cag cag tat 1537 Gln Asp Ala Asp Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr 495 500 505 gca gat gac tgg atg gct ggg gct gtg gct ccc cca gcc cgg cct cct 1585 Ala Asp Asp Trp Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro 510 515 520 cgg cct cca tac cct cct aga agg gat ggt tct ggg ggc aaa gga gga 1633 Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly 525 530 535 540 ggt ggc agt gcc cgc tac aac cag ggc cgg agc agg agt ggg ggg gca 1681 Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala 545 550 555 tct att ggt ttt cac acc caa acc atc ctc att ctc tcc ctc tca gcc 1729 Ser Ile Gly Phe His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala 560 565 570 ctg gcc ctg ctt gga cct cga ctcgagggca agggcgaatt ccagca 1776 Leu Ala Leu Leu Gly Pro Arg 575 60 579 PRT Homo sapiens 60 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg 385 390 395 400 Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser 405 410 415 Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly 420 425 430 Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala 435 440 445 Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp 450 455 460 Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg 465 470 475 480 Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp 485 490 495 Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp 500 505 510 Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr 515 520 525 Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala 530 535 540 Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe 545 550 555 560 His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu 565 570 575 Gly Pro Arg 61 1785 DNA Homo sapiens CDS (1)..(1737) 61 atg tcc gcg ctg cga cct ctc ctg ctt ctg ctg ctg cct ctg tgt ccc 48 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 ggt cct ggt ccc gga ccc ggg agc gag gca aag gtc acc cgg agt tgt 96 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 gca gag acc cgg cag gtg ctg ggg gcc cgg gga tat agc tta aac cta 144 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 atc cct ccc gcc ctg atc tca ggt gag cac ctc cgg gtc tgt ccc cag 192 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 gag tac acc tgc tgt tcc agt gag aca gag cag agg ctg atc agg gag 240 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 act gag gcc acc ttc cga ggc ctg gtg gag gac agc ggc tcc ttt ctg 288 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 gtt cac aca ctg gct gcc agg cac aga aaa ttt gat gag ttt ttt ctg 336 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 gag atg ctc tca gta gcc cag cac tct ctg acc cag ctc ttc tcc cac 384 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 tcc tac ggc cgc ctg tat gcc cag cac gcc ctc ata ttc aat ggc ctg 432 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 ttc tct cgg ctg cga gac ttc tat ggg gaa tct ggt gag ggg ttg gat 480 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 gac acc ctg gcg gat ttc tgg gca cag ctc ctg gag aga gtg ttc ccg 528 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 ctg ctg cac cca cag tac agc ttc ccc cct gac tac ctg ctc tgc ctc 576 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 tca cgc ttg gcc tca tct acc gat ggc tct ctg cag ccc ttt ggg gac 624 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 tca ccc cgc cgc ctc cgc ctg cag ata acc cgg acc ctg gtg gct gcc 672 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 cga gcc ttt gtg cag ggc ctg gag act gga aga aat gtg gtc agc gaa 720 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 gcg ctt aag gtt ccg gtg tct gaa ggc tgc agc cag gct ctg atg cgt 768 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 ctc atc ggc tgt ccc ctg tgc cgg ggg gtc ccc tca ctt atg ccc tgc 816 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 cag ggc ttc tgc ctc aac gtg gtt cgt ggc tgt ctc agc agc agg gga 864 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 ctg gag cct gac tgg ggc aac tat ctg gat ggt ctc ctg atc ctg gct 912 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 gat aag ctc cag ggc ccc ttt tcc ttt gag ctg acg gcc gag tcc att 960 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 ggg gtg aag atc tcg gag ggt ttg atg tac ctg cag gaa aac agt gcg 1008 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 aag gtg tcc gcc cag gta ttt cag gag tgc ggc ccc ccc gac ccg gtg 1056 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 cct gcc cgc aac cgt cga gcc ccg ccg ccc cgg gaa gag gcg ggc cgg 1104 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 ctg tgg tcg atg gtg acc gag gag gag cgg cca acg acc gcc gca ggc 1152 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 acc aac ctg cac cgg ctg gtg tgg gag ctc cgc gag cgt ctg gcc cgg 1200 Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg 385 390 395 400 atg cgg ggc ttc tgg gcc cgg ctg tcc ctg acg gtg tgc gga gac tct 1248 Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser 405 410 415 cgc atg gca gcg gac gcc tcg ctg gag gcg gcg ccc tgc tgg acc gga 1296 Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly 420 425 430 gcc ggg cgg ggc cgg tac ttg ccg cca gtg gtc ggg ggc tcc ccg gcc 1344 Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala 435 440 445 gag cag gtc aac aac ccc gag ctc aag gtg gac gcc tcg ggc ccc gat 1392 Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp 450 455 460 gtc ccg aca cgg cgg cgt cgg cta cag ctc cgg gcg gcc acg gcc aga 1440 Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg 465 470 475 480 atg aaa acg gcc gca ctg gga cac gac ctg gac ggg cag gac gca gat 1488 Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp 485 490 495 gag gat gcc agc ggc tct gga ggg gga cag cag tat gca gat gac tgg 1536 Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp 500 505 510 atg gct ggg gct gtg gct ccc cca gcc cgg cct cct cgg cct cca tac 1584 Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr 515 520 525 cct cct aga agg gat ggt tct ggg ggc aaa gga gga ggt ggc agt gcc 1632 Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala 530 535 540 cgc tac aac cag ggc cgg agc agg agt ggg ggg gca tct att ggt ttt 1680 Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe 545 550 555 560 cac acc caa acc atc ctc att ctc tcc ctc tca gcc ctg gcc ctg ctt 1728 His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu 565 570 575 gga cct cga taacggggga ggggtgccct agcatcagaa gggttcatgg ccctttcc 1785 Gly Pro Arg 62 579 PRT Homo sapiens 62 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg 385 390 395 400 Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser 405 410 415 Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly 420 425 430 Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala 435 440 445 Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp 450 455 460 Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg 465 470 475 480 Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp 485 490 495 Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp 500 505 510 Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr 515 520 525 Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala 530 535 540 Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe 545 550 555 560 His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu 565 570 575 Gly Pro Arg 63 1648 DNA Homo sapiens CDS (2)..(1648) 63 c acc gga tcc agc gag gca aag gtc acc cgg agt tgt gca gag acc cgg 49 Thr Gly Ser Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr Arg 1 5 10 15 cag gtg ctg ggg gcc cgg gga tat agc tta aac cta atc cct ccc gcc 97 Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro Ala 20 25 30 ctg atc tca ggt gag cac ctc cgg gtc tgt ccc cag gag tac acc tgc 145 Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr Cys 35 40 45 tgt tcc agt gag aca gag cag agg ctg atc agg gag act gag gcc acc 193 Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala Thr 50 55 60 ttc cga ggc ctg gtg gag gac agc ggc tcc ttt ctg gtt cac aca ctg 241 Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr Leu 65 70 75 80 gct gcc agg cac aga aaa ttt gat gag ttt ttt ctg gag atg ctc tca 289 Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu Ser 85 90 95 gta gcc cag cac tct ctg acc cag ctc ttc tcc cac tcc tac ggc cgc 337 Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly Arg 100 105 110 ctg tat gcc cag cac gcc ctc ata ttc aat ggc ctg ttc tct cgg ctg 385 Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg Leu 115 120 125 cga gac ttc tat ggg gaa tct ggt gag ggg ttg gat gac acc ctg gcg 433 Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu Ala 130 135 140 gat ttc tgg gca cag ctc ctg gag aga gtg ttc ccg ctg ctg cac cca 481 Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His Pro 145 150 155 160 cag tac agc ttc ccc cct gac tac ctg ctc tgc ctc tca cgc ttg gcc 529 Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu Ala 165 170 175 tca tct acc gat ggc tct ctg cag ccc ttt ggg gac tca ccc cgc cgc 577 Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg Arg 180 185 190 ctc cgc ctg cag ata acc cgg acc ctg gtg gct gcc cga gcc ttt gtg 625 Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe Val 195 200 205 cag ggc ctg gag act gga aga aat gtg gtc agc gaa gcg ctt aag gtg 673 Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys Val 210 215 220 ccg gtg tct gaa ggc tgc agc cag gct ctg atg cgt ctc atc ggc tgt 721 Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly Cys 225 230 235 240 ccc ctg tgc cgg ggg gtc ccc tca ctt atg ccc tgc cag ggc ttc tgc 769 Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe Cys 245 250 255 ctc aac gtg gtt cgt ggc tgt ctc agc agc agg gga ctg gag cct gac 817 Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro Asp 260 265 270 tgg ggc aac tat ctg gat ggt ctc ctg atc ctg gct gat aag ctc cag 865 Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu Gln 275 280 285 ggc ccc ttt tcc ttt gag ctg acg gcc gag tcc att ggg gtg aag atc 913 Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys Ile 290 295 300 tcg gag ggt ttg atg tac ctg cag gaa aac agt gcg aag gtg tcc gcc 961 Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser Ala 305 310 315 320 cag gtg ttt cag gag tgc ggc ccc ccc gac ccg gtg cct gcc cgc aac 1009 Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg Asn 325 330 335 cgt cga gcc ccg ccg ccc cgg gaa gag gcg ggc cgg ctg tgg tcg atg 1057 Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser Met 340 345 350 gtg acc gag gag gag cgg ccc acg acg gcc gca ggc acc aac ctg cac 1105 Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu His 355 360 365 cgg ctg gtg tgg gag ctc cgc gag cgt ctg gcc cgg atg cgg ggc ttc 1153 Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg Met Arg Gly Phe 370 375 380 tgg gcc cgg ctg tcc ctg acg gtg tgc gga gac tct cgc atg gca gcg 1201 Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser Arg Met Ala Ala 385 390 395 400 gac gcc tcg ctg gag gcg gcg ccc tgc tgg acc gga gcc ggg cgg ggc 1249 Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly Ala Gly Arg Gly 405 410 415 cgg tac ttg ccg cca gtg gtc ggg ggc tcc ccg gcc gag cag gtc aac 1297 Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala Glu Gln Val Asn 420 425 430 aac ccc gag ctc aag gtg gac gcc tcg ggc ccc gat gtc ccg aca cgg 1345 Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp Val Pro Thr Arg 435 440 445 cgg cgt cgg cta cag ctc cgg gcg gcc acg gcc aga atg aaa acg gcc 1393 Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg Met Lys Thr Ala 450 455 460 gca ctg gga cac gac ctg gac ggg cag gac gcg gat gag gat gcc agc 1441 Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp Glu Asp Ala Ser 465 470 475 480 ggc tct gga ggg gga cag cag tat gca gat gac tgg atg gct ggg gct 1489 Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp Met Ala Gly Ala 485 490 495 gtg gct ccc cca gcc cgg cct cct cgg cct cca tac cct cct aga agg 1537 Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro Arg Arg 500 505 510 gat ggt tct ggg ggc aaa gga gga ggt ggc agt gcc cgc tac aac cag 1585 Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr Asn Gln 515 520 525 ggc cgg agc agg agt ggg ggg gca tct att ggt ttt cac acc caa acc 1633 Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe His Thr Gln Thr 530 535 540 atc ctc ctc gag ggc 1648 Ile Leu Leu Glu Gly 545 64 549 PRT Homo sapiens 64 Thr Gly Ser Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr Arg 1 5 10 15 Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro Ala 20 25 30 Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr Cys 35 40 45 Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala Thr 50 55 60 Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr Leu 65 70 75 80 Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu Ser 85 90 95 Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly Arg 100 105 110 Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg Leu 115 120 125 Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu Ala 130 135 140 Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His Pro 145 150 155 160 Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu Ala 165 170 175 Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg Arg 180 185 190 Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe Val 195 200 205 Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys Val 210 215 220 Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly Cys 225 230 235 240 Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe Cys 245 250 255 Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro Asp 260 265 270 Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu Gln 275 280 285 Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys Ile 290 295 300 Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser Ala 305 310 315 320 Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg Asn 325 330 335 Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser Met 340 345 350 Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu His 355 360 365 Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg Met Arg Gly Phe 370 375 380 Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser Arg Met Ala Ala 385 390 395 400 Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly Ala Gly Arg Gly 405 410 415 Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala Glu Gln Val Asn 420 425 430 Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp Val Pro Thr Arg 435 440 445 Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg Met Lys Thr Ala 450 455 460 Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp Glu Asp Ala Ser 465 470 475 480 Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp Met Ala Gly Ala 485 490 495 Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro Arg Arg 500 505 510 Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr Asn Gln 515 520 525 Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe His Thr Gln Thr 530 535 540 Ile Leu Leu Glu Gly 545 65 1613 DNA Homo sapiens CDS (1)..(1347) 65 atg tcc gcg ctg cga cct ctc ctg ctt ctg ctg ctg cct ctg tgt ccc 48 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 ggt cct ggt ccc gga ccc ggg agc gag gca aag gtc acc cgg agt tgt 96 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 gca gag acc cgg cag gtg ctg ggg gcc cgg gga tat agc tta aac cta 144 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 atc cct ccc gcc ctg atc tca ggt gag cac ctc cgg gtc tgt ccc cag 192 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 gag tac acc tgc tgt tcc agt gag aca gag cag agg ctg atc agg gag 240 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 act gag gcc acc ttc cga ggc ctg gtg gag gac agc ggc tcc ttt ctg 288 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 gtt cac aca ctg gct gcc agg cac aga aaa ttt gat gag ttt ttt ctg 336 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 gag atg ctc tca gta gcc cag cac tct ctg acc cag ctc ttc tcc cac 384 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 tcc tac ggc cgc ctg tat gcc cag cac gcc ctc ata ttc aat ggc ctg 432 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 ttc tct cgg ctg cga gac ttc tat ggg gaa tct ggt gag ggg ttg gat 480 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 gac acc ctg gcg gat ttc tgg gca cag ctc ctg gag aga gtg ttc ccg 528 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 ctg ctg cac cca cag tac agc ttc ccc cct gac tac ctg ctc tgc ctc 576 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 tca cgc ttg gcc tca tct acc gat ggc tct ctg cag ccc ttt ggg gac 624 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 tca ccc cgc cgc ctc cgc ctg cag ata acc cgg acc ctg gtg gct gcc 672 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 cga gcc ttt gtg cag ggc ctg gag act gga aga aat gtg gtc agc gaa 720 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 gcg ctt aag gtg ccg gtg tct gaa ggc tgc agc cag gct ctg atg cgt 768 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 ctc atc ggc tgt ccc ctg tgc cgg ggg gtc ccc tca ctt atg ccc tgc 816 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 cag ggc ttc tgc ctc aac gtg gtt cgt ggc tgt ctc agc agc agg gga 864 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 ctg gag cct gac tgg ggc aac tat ctg gat ggt ctc ctg atc ctg gct 912 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 gat aag ctc cag ggc ccc ttt tcc ttt gag ctg acg gcc gag tcc att 960 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 ggg gtg aag atc tcg gag ggt ttg atg tac ctg cag gaa aac agt gcg 1008 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 aag gtg tcc gcc cag gtg ttt cag gag tgc ggc ccc ccc gac ccg gtg 1056 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 cct gcc cgc aac cgt cga gcc ccg ccg ccc cgg gaa gag gcg ggc cgg 1104 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 ctg tgg tcg atg gtg acc gag gag gag cgg ccc acg acg gcc gca ggc 1152 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 acc aac ctg cac cgg ctg gta ctt gcc gcc agt ggt cgg ggg ctc ccc 1200 Thr Asn Leu His Arg Leu Val Leu Ala Ala Ser Gly Arg Gly Leu Pro 385 390 395 400 ggc cga gca ggt caa caa ccc cga gct caa ggt gga cgc ctc ggg ccc 1248 Gly Arg Ala Gly Gln Gln Pro Arg Ala Gln Gly Gly Arg Leu Gly Pro 405 410 415 cga tgt ccc gac acg gcg gcg tcg gct aca gct ccg ggc ggc cac ggc 1296 Arg Cys Pro Asp Thr Ala Ala Ser Ala Thr Ala Pro Gly Gly His Gly 420 425 430 cag aat gaa aac ggc cgc act ggg aca cga cct gga cgg gca gga cgc 1344 Gln Asn Glu Asn Gly Arg Thr Gly Thr Arg Pro Gly Arg Ala Gly Arg 435 440 445 gga tgaggatgcc agcggctctg gagggggaca gcagtatgca gatgactgga 1397 Gly tggctggggc tgtggctccc ccagcccggc ctcctcggcc tccataccct cctagaaggg 1457 atggttctgg gggcaaagga ggaggtggca gtgcccgcta caaccagggc cggagcagga 1517 gtgggggggc atctattggt tttcacaccc aaaccatcct cattctctcc ctctcagacc 1577 tggccctgct tggacctcga taacggggga ggggtg 1613 66 449 PRT Homo sapiens 66 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 Thr Asn Leu His Arg Leu Val Leu Ala Ala Ser Gly Arg Gly Leu Pro 385 390 395 400 Gly Arg Ala Gly Gln Gln Pro Arg Ala Gln Gly Gly Arg Leu Gly Pro 405 410 415 Arg Cys Pro Asp Thr Ala Ala Ser Ala Thr Ala Pro Gly Gly His Gly 420 425 430 Gln Asn Glu Asn Gly Arg Thr Gly Thr Arg Pro Gly Arg Ala Gly Arg 435 440 445 Gly 67 1297 DNA Homo sapiens CDS (2)..(1297) 67 c acc gga tcc acc agc gag gca aag gtc acc cgg agt tgt gca gag acc 49 Thr Gly Ser Thr Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr 1 5 10 15 cgg cag gtg ctg ggg gcc cgg gga tat agc tta aac cta atc cct ccc 97 Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro 20 25 30 gcc ctg atc tca ggt gag cac ctc cgg gtc tgt ccc cag gag tac acc 145 Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr 35 40 45 tgc tgt tcc agt gag aca gag cag agg ctg atc agg gag act gag gcc 193 Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala 50 55 60 acc ttc cga ggc ctg gtg gag gac agc ggc tcc ttt ctg gtt cac aca 241 Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr 65 70 75 80 ctg gct gcc agg cac aga aaa ttt gat gag ttt ttt ctg gag atg ctc 289 Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu 85 90 95 tca gta gcc cag cac tct ctg acc cag ctc ttc tcc cac tcc tac ggc 337 Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly 100 105 110 cgc ctg tat gcc cag cac gcc ctc ata ttc aat ggc ctg ttc tct cgg 385 Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg 115 120 125 ctg cga gac ttc tat ggg gaa tct ggt gag ggg ttg gat gac acc ctg 433 Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu 130 135 140 gcg gat ttc tgg gca cag ctc ctg gag aga gtg ttc ccg ctg ctg cac 481 Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His 145 150 155 160 cca cag tac agc ttc ccc cct gac tac ctg ctc tgc ctc tca cgc ttg 529 Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu 165 170 175 gcc tca tct acc gat ggc tct ctg cag ccc ttt ggg gac tca ccc cgc 577 Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg 180 185 190 cgc ctc cgc ctg cag ata acc cgg acc ctg gtg gct gcc cga gcc ttt 625 Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe 195 200 205 gtg cag ggc ctg gag act gga aga aat gtg gtc agc gaa gcg ctt aag 673 Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys 210 215 220 gtg ccg gtg tct gaa ggc tgc agc cag gct ctg atg cgt ctc atc ggc 721 Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly 225 230 235 240 tgt ccc ctg tgc cgg ggg gtc ccc tca ctt atg ccc tgc cag ggc ttc 769 Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe 245 250 255 tgc ctc aac gtg gtt cgt ggc tgt ctc agc agc agg gga ctg gag cct 817 Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro 260 265 270 gac tgg ggc aac tat ctg gat ggt ctc ctg atc ctg gct gat aag ctc 865 Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu 275 280 285 cag ggc ccc ttt tcc ttt gag ctg acg gcc gag tcc att ggg gtg aag 913 Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys 290 295 300 atc tcg gag ggt ttg atg tac ctg cag gaa aac agt gcg aag gtg tcc 961 Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser 305 310 315 320 gcc cag gtg ttt cag gag tgc ggc ccc ccc gac ccg gtg cct gcc cgc 1009 Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg 325 330 335 aac cgt cga gcc ccg ccg ccc cgg gaa gag gcg ggc cgg ctg tgg tcg 1057 Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser 340 345 350 atg gtg acc gag gag gag cgg ccc acg acg gcc gca ggc acc aac ctg 1105 Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu 355 360 365 cac cgg ctg gta ctt gcc gcc agt ggt cgg ggg ctc ccc ggc cga gca 1153 His Arg Leu Val Leu Ala Ala Ser Gly Arg Gly Leu Pro Gly Arg Ala 370 375 380 ggt caa caa ccc cga gct caa ggt gga cgc ctc ggg ccc cga tgt ccc 1201 Gly Gln Gln Pro Arg Ala Gln Gly Gly Arg Leu Gly Pro Arg Cys Pro 385 390 395 400 gac acg gcg gcg tcg gct aca gct ccg ggc ggc cac ggc cag aat gaa 1249 Asp Thr Ala Ala Ser Ala Thr Ala Pro Gly Gly His Gly Gln Asn Glu 405 410 415 aac ggc cgc act ggg aca cga cct gga cgg gca gga cgc gga ctc gag 1297 Asn Gly Arg Thr Gly Thr Arg Pro Gly Arg Ala Gly Arg Gly Leu Glu 420 425 430 68 432 PRT Homo sapiens 68 Thr Gly Ser Thr Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr 1 5 10 15 Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro 20 25 30 Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr 35 40 45 Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala 50 55 60 Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr 65 70 75 80 Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu 85 90 95 Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly 100 105 110 Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg 115 120 125 Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu 130 135 140 Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His 145 150 155 160 Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu 165 170 175 Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg 180 185 190 Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe 195 200 205 Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys 210 215 220 Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly 225 230 235 240 Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe 245 250 255 Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro 260 265 270 Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu 275 280 285 Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys 290 295 300 Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser 305 310 315 320 Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg 325 330 335 Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser 340 345 350 Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu 355 360 365 His Arg Leu Val Leu Ala Ala Ser Gly Arg Gly Leu Pro Gly Arg Ala 370 375 380 Gly Gln Gln Pro Arg Ala Gln Gly Gly Arg Leu Gly Pro Arg Cys Pro 385 390 395 400 Asp Thr Ala Ala Ser Ala Thr Ala Pro Gly Gly His Gly Gln Asn Glu 405 410 415 Asn Gly Arg Thr Gly Thr Arg Pro Gly Arg Ala Gly Arg Gly Leu Glu 420 425 430 69 1126 DNA Homo sapiens CDS (2)..(1126) 69 c acc gga tcc acc agc gag gca aag gtc acc cgg agt tgt gca gag acc 49 Thr Gly Ser Thr Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr 1 5 10 15 cgg cag gtg ctg ggg gcc cgg gga tat agc tta aac cta atc cct ccc 97 Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro 20 25 30 gcc ctg atc tca ggt gag cac ctc cgg gtc tgt ccc cag gag tac acc 145 Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr 35 40 45 tgc tgt tcc agt gag aca gag cag agg ctg atc agg gag act gag gcc 193 Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala 50 55 60 acc ttc cga ggc ctg gtg gag gac agc ggc tcc ttt ctg gtt cac aca 241 Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr 65 70 75 80 ctg gct gcc agg cac aga aaa ttt gat gag ttt ttt ctg gag atg ctc 289 Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu 85 90 95 tca gta gcc cag cac tct ctg acc cag ctc ttc tcc cac tcc tac ggc 337 Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly 100 105 110 cgc ctg tat gcc cag cac gcc ctc ata ttc aat ggc ctg ttc tct cgg 385 Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg 115 120 125 ctg cga gac ttc tat ggg gaa tct ggt gag ggg ttg gat gac acc ctg 433 Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu 130 135 140 gcg gat ttc tgg gca cag ctc ctg gag aga gtg ttc ccg ctg ctg cac 481 Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His 145 150 155 160 cca cag tac agc ttc ccc cct gac tac ctg ctc tgc ctc tca cgc ttg 529 Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu 165 170 175 gcc tca tct acc gat ggc tct ctg cag ccc ttt ggg gac tca ccc cgc 577 Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg 180 185 190 cgc ctc cgc ctg cag ata acc cgg acc ctg gtg gct gcc cga gcc ttt 625 Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe 195 200 205 gtg cag ggc ctg gag act gga aga aat gtg gtc agc gaa gcg ctt aag 673 Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys 210 215 220 gtg ccg gtg tct gaa ggc tgc agc cag gct ctg atg cgt ctc atc ggc 721 Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly 225 230 235 240 tgt ccc ctg tgc cgg ggg gtc ccc tca ctt atg ccc tgc cag ggc ttc 769 Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe 245 250 255 tgc ctc aac gtg gtt cgt ggc tgt ctc agc agc agg gga ctg gag cct 817 Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro 260 265 270 gac tgg ggc aac tat ctg gat ggt ctc ctg atc ctg gct gat aag ctc 865 Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu 275 280 285 cag ggc ccc ttt tcc ttt gag ctg acg gcc gag tcc att ggg gtg aag 913 Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys 290 295 300 atc tcg gag ggt ttg atg tac ctg cag gaa aac agt gcg aag gtg tcc 961 Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser 305 310 315 320 gcc cag gtg ttt cag gag tgc ggc ccc ccc gac ccg gtg cct gcc cgc 1009 Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg 325 330 335 aac cgt cga gcc ccg ccg ccc cgg gaa gag gcg ggc cgg ctg tgg tcg 1057 Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser 340 345 350 atg gtg acc gag gag gag cgg ccc acg acg gcc gca ggc acc aac ctg 1105 Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu 355 360 365 cac cgg ctg gta ctt ctc gag 1126 His Arg Leu Val Leu Leu Glu 370 375 70 375 PRT Homo sapiens 70 Thr Gly Ser Thr Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr 1 5 10 15 Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro 20 25 30 Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr 35 40 45 Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala 50 55 60 Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr 65 70 75 80 Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu 85 90 95 Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly 100 105 110 Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg 115 120 125 Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu 130 135 140 Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His 145 150 155 160 Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu 165 170 175 Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg 180 185 190 Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe 195 200 205 Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys 210 215 220 Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly 225 230 235 240 Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe 245 250 255 Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro 260 265 270 Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu 275 280 285 Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys 290 295 300 Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser 305 310 315 320 Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg 325 330 335 Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser 340 345 350 Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu 355 360 365 His Arg Leu Val Leu Leu Glu 370 375 71 1776 DNA Homo sapiens 71 caccggatcc accatgtccg cgctgcgacc tctcctgctt ctgctgctgc ctctgtgtcc 60 cggtcctggt cccggacccg ggagcgaggc aaaggtcacc cggagttgtg cagagacccg 120 gcaggtgctg ggggcccggg gatatagctt aaacctaatc cctcccgccc tgatctcagg 180 tgagcacctc cgggtctgtc cccaggagta cacctgctgt tccagtgaga cagagcagag 240 gctgatcagg gagactgagg ccaccttccg aggcctggtg gaggacagcg gctcctttct 300 ggttcacaca ctggctgcca ggcacagaaa atttgatgag ttttttctgg agatgctctc 360 agtagcccag cactctctga cccagctctt ctcccactcc tacggccgcc tgtatgccca 420 gcacgccctc atattcaatg gcctgttctc tcggctgcga gacttctatg gggaatctgg 480 tgaggggttg gatgacaccc tggcggattt ctgggcacag ctcctggaga gagtgttccc 540 gctgctgcac ccacagtaca gcttcccccc tgactacctg ctctgcctct cacgcttggc 600 ctcatctacc gatggctctc tgcagccctt tggggactca ccccgccgcc tccgcctgca 660 gataacccgg accctggtgg ctgcccgagc ctttgtgcag ggcctggaga ctggaagaaa 720 tgtggtcagc gaagcgctta aggtgccggt gtctgaaggc tgcagccagg ctctgatgcg 780 tctcatcggc tgtcccctgt gccggggggt cccctcactt atgccctgcc agggcttctg 840 cctcaacgtg gttcgtggct gtctcagcag caggggactg gagcctgact ggggcaacta 900 tctggatggt ctcctgatcc tggctgataa gctccagggc cccttttcct ttgagctgac 960 ggccgagtcc attggggtga agatctcgga gggtttgatg tacctgcagg aaaacagtgc 1020 gaaggtgtcc gcccaggtgt ttcaggagtg cggccccccc gacccggtgc ctgcccgcaa 1080 ccgtcgagcc ccgccgcccc gggaagaggc gggccggctg tggtcgatgg tgaccgagga 1140 ggagcggccc acgacggccg caggcaccaa cctgcaccgg ctggtgtggg agctccgcga 1200 gcgtctggcc cggatgcggg gcttctgggc ccggctgtcc ctgacggtgt gcggagactc 1260 tcgcatggca gcggacgcct cgctggaggc ggcgccctgc tggaccggag ccgggcgggg 1320 ccggtacttg ccgccagtgg tcgggggctc cccggccgag caggtcaaca accccgagct 1380 caaggtggac gcctcgggcc ccgatgtccc gacacggcgg cgtcgactac agctccgggc 1440 ggccacggcc agaatgaaaa cggccgcact gggacacgac ctggacgggc aggacgcgga 1500 tgaggatgcc agcggctctg gagggggaca gcagtatgca gatgactgga tggctggggc 1560 tgtggctccc ccagcccggc ctcctcggcc tccataccct cctagaaggg atggttctgg 1620 gggcaaagga ggaggtggca gtgcccgcta caaccagggc cggagcagga gtgggggggc 1680 atctattggt tttcacaccc aaaccatcct cattctctcc ctctcagccc tggccctgct 1740 tggacctcga ctcgagggca agggcgaatt ccagca 1776 72 592 PRT Homo sapiens misc_feature (592)..(592) Wherein Xaa may be any naturally occurring amino acid 72 Thr Gly Ser Thr Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu 1 5 10 15 Pro Leu Cys Pro Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val 20 25 30 Thr Arg Ser Cys Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr 35 40 45 Ser Leu Asn Leu Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg 50 55 60 Val Cys Pro Gln Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg 65 70 75 80 Leu Ile Arg Glu Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser 85 90 95 Gly Ser Phe Leu Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp 100 105 110 Glu Phe Phe Leu Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln 115 120 125 Leu Phe Ser His Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile 130 135 140 Phe Asn Gly Leu Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly 145 150 155 160 Glu Gly Leu Asp Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu 165 170 175 Arg Val Phe Pro Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr 180 185 190 Leu Leu Cys Leu Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln 195 200 205 Pro Phe Gly Asp Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr 210 215 220 Leu Val Ala Ala Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn 225 230 235 240 Val Val Ser Glu Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln 245 250 255 Ala Leu Met Arg Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser 260 265 270 Leu Met Pro Cys Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu 275 280 285 Ser Ser Arg Gly Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu 290 295 300 Leu Ile Leu Ala Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr 305 310 315 320 Ala Glu Ser Ile Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln 325 330 335 Glu Asn Ser Ala Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro 340 345 350 Pro Asp Pro Val Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu 355 360 365 Glu Ala Gly Arg Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr 370 375 380 Thr Ala Ala Gly Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu 385 390 395 400 Arg Leu Ala Arg Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val 405 410 415 Cys Gly Asp Ser Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro 420 425 430 Cys Trp Thr Gly Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly 435 440 445 Gly Ser Pro Ala Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala 450 455 460 Ser Gly Pro Asp Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala 465 470 475 480 Ala Thr Ala Arg Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly 485 490 495 Gln Asp Ala Asp Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr 500 505 510 Ala Asp Asp Trp Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro 515 520 525 Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly 530 535 540 Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala 545 550 555 560 Ser Ile Gly Phe His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala 565 570 575 Leu Ala Leu Leu Gly Pro Arg Leu Glu Gly Lys Gly Glu Phe Gln Xaa 580 585 590 73 3755 DNA Homo sapiens 73 caccggatcc accatgtccg cgctgcgacc tctcctgctt ctgctgctgc ctctgtgtcc 60 cggtcctggt cccggacccg ggagcgaggc aaaggtcacc cggagttgtg cagagacccg 120 gcaggtgctg ggggcccggg gatatagctt aaacctaatc cctcccgccc tgatctcagg 180 tgagcacctc cgggtctgtc cccaggagta cacctgctgt tccagtgaga cagagcagag 240 gctgatcagg gagactgagg ccaccttccg aggcctggtg gaggacagcg gctcctttct 300 ggttcacaca ctggctgcca ggcacagaaa atttgatgag ttttttctgg agatgctctc 360 agtagcccag cactctctga cccagctctt ctcccactcc tacggccgcc tgtatgccca 420 gcacgccctc atattcaatg gcctgttctc tcggctgcga gacttctatg gggaatctgg 480 tgaggggttg gatgacaccc tggcggattt ctgggcacag ctcctggaga gagtgttccc 540 gctgctgcac ccacagtaca gcttcccccc tgactacctg ctctgcctct cacgcttggc 600 ctcatctacc gatggctctc tgcagccctt tggggactca ccccgccgcc tccgcctgca 660 gataacccgg accctggtgg ctgcccgagc ctttgtgcag ggcctggaga ctggaagaaa 720 tgtggtcagc gaagcgctta aggtgccggt gtctgaaggc tgcagccagg ctctgatgcg 780 tctcatcggc tgtcccctgt gccggggggt cccctcactt atgccctgcc agggcttctg 840 cctcaacgtg gttcgtggct gtctcagcag caggggactg gagcctgact ggggcaacta 900 tctggatggt ctcctgatcc tggctgataa gctccagggc cccttttcct ttgagctgac 960 ggccgagtcc attggggtga agatctcgga gggtttgatg tacctgcagg aaaacagtgc 1020 gaaggtgtcc gcccaggtgt ttcaggagtg cggccccccc gacccggtgc ctgcccgcaa 1080 ccgtcgagcc ccgccgcccc gggaagaggc gggccggctg tggtcgatgg tgaccgagga 1140 ggagcggccc acgacggccg caggcaccaa cctgcaccgg ctggtgtggg agctccgcga 1200 gcgtctggcc cggatgcggg gcttctgggc ccggctgtcc ctgacggtgt gcggagactc 1260 tcgcatggca gcggacgcct cgctggaggc ggcgccctgc tggaccggag ccgggcgggg 1320 ccggtacttg ccgccagtgg tcgggggctc cccggccgag caggtcaaca accccgagct 1380 caaggtggac gcctcgggcc ccgatgtccc gacacggcgg cgtcgactac agctccgggc 1440 ggccacggcc agaatgaaaa cggccgcact gggacacgac ctggacgggc aggacgcgga 1500 tgaggatgcc agcggctctg gagggggaca gcagtatgca gatgactgga tggctggggc 1560 tgtggctccc ccagcccggc ctcctcggcc tccataccct cctagaaggg atggttctgg 1620 gggcaaagga ggaggtggca gtgcccgcta caaccagggc cggagcagga gtgggggggc 1680 atctattggt tttcacaccc aaaccatcct cattctctcc ctctcagccc tggccctgct 1740 tggacctcga ctcgagggca agggcgaatt ccagcatgag gctctgcttt cctccttagg 1800 acccactttg ccgtcctggg gtggctgcag ttatgtccgc gctgcgacct ctcctgcttc 1860 tgctgctgcc tctgtgtccc ggtcctggtc ccggacccgg gagcgaggca aaggtcaccc 1920 ggagttgtgc agagacccgg caggtgctgg gggcccgggg atatagctta aacctaatcc 1980 ctcccgccct gatctcaggt gagcacctcc gggtctgtcc ccaggagtac acctgctgtt 2040 ccagtgagac agagcagagg ctgatcaggg agactgaggc caccttccga ggcctggtgg 2100 aggacagcgg ctcctttctg gttcacacac tggctgccag gcacagaaaa tttgatgagt 2160 tttttctgga gatgctctca gtagcccagc actctctgac ccagctcttc tcccactcct 2220 acggccgcct gtatgcccag cacgccctca tattcaatgg cctgttctct cggctgcgag 2280 acttctatgg ggaatctggt gaggggttgg atgacaccct ggcggatttc tgggcacagc 2340 tcctggagag agtgttcccg ctgctgcacc cacagtacag cttcccccct gactacctgc 2400 tctgcctctc acgcttggcc tcatctaccg atggctctct gcagcccttt ggggactcac 2460 cccgccgcct ccgcctgcag ataacccgga ccctggtggc tgcccgagcc tttgtgcagg 2520 gcctggagac tggaagaaat gtggtcagcg aagcgcttaa ggttccggtg tctgaaggct 2580 gcagccaggc tctgatgcgt ctcatcggct gtcccctgtg ccggggggtc ccctcactta 2640 tgccctgcca gggcttctgc ctcaacgtgg ttcgtggctg tctcagcagc aggggactgg 2700 agcctgactg gggcaactat ctggatggtc tcctgatcct ggctgataag ctccagggcc 2760 ccttttcctt tgagctgacg gccgagtcca ttggggtgaa gatctcggag ggtttgatgt 2820 acctgcagga aaacagtgcg aaggtgtccg cccaggtatt tcaggagtgc ggcccccccg 2880 acccggtgcc tgcccgcaac cgtcgagccc cgccgccccg ggaagaggcg ggccggctgt 2940 ggtcgatggt gaccgaggag gagcggccaa gcgcagatga ggatgccagc ggctctggag 3000 ggggacagca gtatgcagat gactggatgg ctggggctgt ggctccccca gcccggcctc 3060 ctcggcctcc ataccctcct agaagggatg gttctggggg caaaggagga ggtggcagtg 3120 cccgctacaa ccagggccgg agcaggagtg ggggggcatc tattggtttt cacacccaaa 3180 ccatcctcat tctctccctc tcagccctgg ccctgcttgg acctcgataa cgggggaggg 3240 gtgccctagc atcagaaggg ttcatggccc tttcccctcc tcccccctca gctgggcctg 3300 gggaggagtc gaagggggct gcagagaggg tagagaaggg actttgcagg tgaatggctg 3360 gggccccaaa tccaggagat tttcatcaga ggtgggtggg tgttcacaat atttattttt 3420 tcatttggta atgggagggg ggcctggggg tatttattta ggagggagtg tggtttcctt 3480 agaaggtata gtctctagcc ctctaaggct ggggctggtg atcagcccca acagagaaaa 3540 tgaggagttt agagttgcag ctgggttctg ttgagttttt tcagtatcaa tttcttaaac 3600 caaattttaa aaaaaacaag gtgggggggt gctcatctcg tgacctctgc cacccacatc 3660 cttcacaaac tccatgtttc agtgtttgag tccatgttta ttctgcaaat aaatggtaat 3720 gtattagaaa aaaaaaaaaa aaaaaaaaaa aaaaa 3755 74 1057 PRT Homo sapiens misc_feature (592)..(592) Wherein Xaa may be any naturally occurring amino acid 74 Thr Gly Ser Thr Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu 1 5 10 15 Pro Leu Cys Pro Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val 20 25 30 Thr Arg Ser Cys Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr 35 40 45 Ser Leu Asn Leu Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg 50 55 60 Val Cys Pro Gln Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg 65 70 75 80 Leu Ile Arg Glu Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser 85 90 95 Gly Ser Phe Leu Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp 100 105 110 Glu Phe Phe Leu Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln 115 120 125 Leu Phe Ser His Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile 130 135 140 Phe Asn Gly Leu Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly 145 150 155 160 Glu Gly Leu Asp Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu 165 170 175 Arg Val Phe Pro Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr 180 185 190 Leu Leu Cys Leu Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln 195 200 205 Pro Phe Gly Asp Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr 210 215 220 Leu Val Ala Ala Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn 225 230 235 240 Val Val Ser Glu Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln 245 250 255 Ala Leu Met Arg Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser 260 265 270 Leu Met Pro Cys Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu 275 280 285 Ser Ser Arg Gly Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu 290 295 300 Leu Ile Leu Ala Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr 305 310 315 320 Ala Glu Ser Ile Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln 325 330 335 Glu Asn Ser Ala Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro 340 345 350 Pro Asp Pro Val Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu 355 360 365 Glu Ala Gly Arg Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr 370 375 380 Thr Ala Ala Gly Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu 385 390 395 400 Arg Leu Ala Arg Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val 405 410 415 Cys Gly Asp Ser Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro 420 425 430 Cys Trp Thr Gly Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly 435 440 445 Gly Ser Pro Ala Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala 450 455 460 Ser Gly Pro Asp Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala 465 470 475 480 Ala Thr Ala Arg Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly 485 490 495 Gln Asp Ala Asp Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr 500 505 510 Ala Asp Asp Trp Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro 515 520 525 Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly 530 535 540 Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala 545 550 555 560 Ser Ile Gly Phe His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala 565 570 575 Leu Ala Leu Leu Gly Pro Arg Leu Glu Gly Lys Gly Glu Phe Gln Xaa 580 585 590 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 595 600 605 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 610 615 620 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 625 630 635 640 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 645 650 655 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 660 665 670 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 675 680 685 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 690 695 700 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 705 710 715 720 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 725 730 735 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 740 745 750 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 755 760 765 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 770 775 780 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 785 790 795 800 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 805 810 815 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 820 825 830 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 835 840 845 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 850 855 860 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 865 870 875 880 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 885 890 895 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 900 905 910 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 915 920 925 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 930 935 940 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 945 950 955 960 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Ser Ala Asp Glu Asp 965 970 975 Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp Met Ala 980 985 990 Gly Ala Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro 995 1000 1005 Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr 1010 1015 1020 Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe His Thr 1025 1030 1035 1040 Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu Gly Pro 1045 1050 1055 Arg 75 725 DNA Homo sapiens CDS (160)..(687) 75 cgcctggtcc agctatcgtg ctcggtattc agttttccgg agcagcgctc tttctctggc 60 ccgcggaacg gtcccgcggc cgagtaccgg attcccgagt ttgggaggct ctgctttcct 120 ccttaggacc cactttgccg tcctggggtg gctgcagtt atg tcc gcg ctg cga 174 Met Ser Ala Leu Arg 1 5 cct ctc ctg ctt ctg ctg ctg cct ctg tgt ccc ggt cct ggt ccc gga 222 Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro Gly Pro Gly Pro Gly 10 15 20 ccc ggg agc gag gca aag gtc acc cgg agt tgt gca gag acc cgg cag 270 Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr Arg Gln 25 30 35 gtg ctg ggg gcc cgg gga tat agc tta aac cta atc cct ccc gcc ctg 318 Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro Ala Leu 40 45 50 atc tca ggt gag cac ctc cgg gtc tgt ccc cag gag tac acc tgc tgt 366 Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr Cys Cys 55 60 65 tcc agt gag aca gag cag agg ctg atc agg gag act gag gcc acc ttc 414 Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala Thr Phe 70 75 80 85 cga ggc ctg gtg gag gac agc ggc tcc ttt ctg gtt cac aca ctg gct 462 Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr Leu Ala 90 95 100 gcc agg cac aga aaa ttt gat gag ttt ttt ctg gag atg ctc tca gta 510 Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu Ser Val 105 110 115 gcc cgg cct cct cgg cct cca tac cct cct aga agg gat ggt tct ggg 558 Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser Gly 120 125 130 ggc aaa gga gga ggt ggc agt gcc cgc tac aac cag ggc cgg agc agg 606 Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser Arg 135 140 145 agt ggg ggg gca tct att ggt ttt cac acc caa acc atc ctc att ctc 654 Ser Gly Gly Ala Ser Ile Gly Phe His Thr Gln Thr Ile Leu Ile Leu 150 155 160 165 tcc ctc tca gcc ctg gcc ttg ctt gga cct cga taacggggga ggggtgccct 707 Ser Leu Ser Ala Leu Ala Leu Leu Gly Pro Arg 170 175 agcatcagaa gggttcat 725 76 176 PRT Homo sapiens 76 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 Glu Met Leu Ser Val Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro Arg 115 120 125 Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr Asn 130 135 140 Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe His Thr Gln 145 150 155 160 Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu Gly Pro Arg 165 170 175 77 1590 DNA Homo sapiens CDS (1)..(1590) 77 agc gag gca aag gtc acc cgg agt tgt gca gag acc cgg cag gtg ctg 48 Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr Arg Gln Val Leu 1 5 10 15 ggg gcc cgg gga tat agc tta aac cta atc cct ccc gcc ctg atc tca 96 Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro Ala Leu Ile Ser 20 25 30 ggt gag cac ctc cgg gtc tgt ccc cag gag tac acc tgc tgt tcc agt 144 Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr Cys Cys Ser Ser 35 40 45 gag aca gag cag agg ctg atc agg gag act gag gcc acc ttc cga ggc 192 Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala Thr Phe Arg Gly 50 55 60 ctg gtg gag gac agc ggc tcc ttt ctg gtt cac aca ctg gct gcc agg 240 Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr Leu Ala Ala Arg 65 70 75 80 cac aga aaa ttt gat gag ttt ttt ctg gag atg ctc tca gta gcc caa 288 His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu Ser Val Ala Gln 85 90 95 cac tct ctg acc cag ctc ttc tcc cac tcc tac ggc cgc ctg tat gcc 336 His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly Arg Leu Tyr Ala 100 105 110 cag cac gcc ctc ata ttc aat ggc ctg ttc tct cgg ctg cga gac ttc 384 Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg Leu Arg Asp Phe 115 120 125 tat ggg gaa tct ggt gag ggg ttg gat gac acc ctg gcg gat ttc tgg 432 Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu Ala Asp Phe Trp 130 135 140 gca cag ctc ctg gag aga gtg ttc ccg ctg ctg cac cca cag tac agc 480 Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His Pro Gln Tyr Ser 145 150 155 160 ttc ccc cct gac tac ctg ctc tgc ctc tca cgc ttg gcc tca tct acc 528 Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu Ala Ser Ser Thr 165 170 175 gat ggc tct ctg cag ccc ttt ggg gac tca ccc cgc cgc ctc cgc ctg 576 Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg Arg Leu Arg Leu 180 185 190 cag ata acc cgg acc ctg gtg gct gcc cga gcc ttt gtg cag ggc ctg 624 Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe Val Gln Gly Leu 195 200 205 gag act gga aga aat gtg gtc agc gaa gcg ctt aag gtg ccg gtg tct 672 Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys Val Pro Val Ser 210 215 220 gaa ggc tgc agc cag gct ctg atg cgt ctc atc ggc tgt ccc ctg tgc 720 Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly Cys Pro Leu Cys 225 230 235 240 cgg ggg gtc ccc tca ctt atg ccc tgc cag ggc ttc tgc ctc aac gtg 768 Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe Cys Leu Asn Val 245 250 255 gtt cgt ggc tgt ctc agc agc agg gga ctg gag cct gac tgg ggc aac 816 Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro Asp Trp Gly Asn 260 265 270 tat ctg gat ggt ctc ctg atc ctg gct gat aag ctc cag ggc ccc ttt 864 Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu Gln Gly Pro Phe 275 280 285 tcc ttt gag ctg acg gcc gag tcc att ggg gtg aag atc tcg gag ggt 912 Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys Ile Ser Glu Gly 290 295 300 ttg atg tac ctg cag gaa aac agt gcg aag gtg tcc gcc cag gtg ttt 960 Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser Ala Gln Val Phe 305 310 315 320 cag gag tgc ggc ccc ccc gac ccg gtg cct gcc cgc aac cgt cga gcc 1008 Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg Asn Arg Arg Ala 325 330 335 ccg ccg ccc cgg gaa gag gcg ggc cgg ctg tgg tcg atg gtg acc gag 1056 Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser Met Val Thr Glu 340 345 350 gag gag cgg ccc acg acg gcc gca ggc acc aac ctg cac cgg ctg gtg 1104 Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu His Arg Leu Val 355 360 365 tgg gag ctc cgc gag cgt ctg gcc cgg atg cgg ggc ttc tgg gcc cgg 1152 Trp Glu Leu Arg Glu Arg Leu Ala Arg Met Arg Gly Phe Trp Ala Arg 370 375 380 ctg tcc ctg acg gtg tgc gga gac tct cgc atg gca gcg gac gcc tcg 1200 Leu Ser Leu Thr Val Cys Gly Asp Ser Arg Met Ala Ala Asp Ala Ser 385 390 395 400 ctg gag gca gcg ccc tgc tgg acc gga gcc ggg cgg ggc cgg tac ttg 1248 Leu Glu Ala Ala Pro Cys Trp Thr Gly Ala Gly Arg Gly Arg Tyr Leu 405 410 415 ccg cca gtg gtc ggg ggc tcc ccg gcc gag cag gtc aac aac ccc gag 1296 Pro Pro Val Val Gly Gly Ser Pro Ala Glu Gln Val Asn Asn Pro Glu 420 425 430 ctc aac gtg gac gcc tcg ggc ccc gat gtc ccg aca cgg cgg cgt cgg 1344 Leu Asn Val Asp Ala Ser Gly Pro Asp Val Pro Thr Arg Arg Arg Arg 435 440 445 cta cgg ctc cgg gcg gcc acg gcc aga atg aaa acg gcc gca ctg gga 1392 Leu Arg Leu Arg Ala Ala Thr Ala Arg Met Lys Thr Ala Ala Leu Gly 450 455 460 cac gac ctg gac ggg cag gac gcg gat gag gat gcc agc ggc tct gga 1440 His Asp Leu Asp Gly Gln Asp Ala Asp Glu Asp Ala Ser Gly Ser Gly 465 470 475 480 ggg gga cag cag tat gca gat gac tgg atg gct ggg gct gtg gct ccc 1488 Gly Gly Gln Gln Tyr Ala Asp Asp Trp Met Ala Gly Ala Val Ala Pro 485 490 495 cca gcc cgg cct cct cgg cct cca tac cct cct aga agg gat ggt tct 1536 Pro Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser 500 505 510 ggg ggc aaa gga gga ggt ggc agt gcc cgc tac aac cag ggc cgg agc 1584 Gly Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser 515 520 525 agg agt 1590 Arg Ser 530 78 530 PRT Homo sapiens 78 Ser Glu Ala Lys Val Thr Arg Ser Cys Ala Glu Thr Arg Gln Val Leu 1 5 10 15 Gly Ala Arg Gly Tyr Ser Leu Asn Leu Ile Pro Pro Ala Leu Ile Ser 20 25 30 Gly Glu His Leu Arg Val Cys Pro Gln Glu Tyr Thr Cys Cys Ser Ser 35 40 45 Glu Thr Glu Gln Arg Leu Ile Arg Glu Thr Glu Ala Thr Phe Arg Gly 50 55 60 Leu Val Glu Asp Ser Gly Ser Phe Leu Val His Thr Leu Ala Ala Arg 65 70 75 80 His Arg Lys Phe Asp Glu Phe Phe Leu Glu Met Leu Ser Val Ala Gln 85 90 95 His Ser Leu Thr Gln Leu Phe Ser His Ser Tyr Gly Arg Leu Tyr Ala 100 105 110 Gln His Ala Leu Ile Phe Asn Gly Leu Phe Ser Arg Leu Arg Asp Phe 115 120 125 Tyr Gly Glu Ser Gly Glu Gly Leu Asp Asp Thr Leu Ala Asp Phe Trp 130 135 140 Ala Gln Leu Leu Glu Arg Val Phe Pro Leu Leu His Pro Gln Tyr Ser 145 150 155 160 Phe Pro Pro Asp Tyr Leu Leu Cys Leu Ser Arg Leu Ala Ser Ser Thr 165 170 175 Asp Gly Ser Leu Gln Pro Phe Gly Asp Ser Pro Arg Arg Leu Arg Leu 180 185 190 Gln Ile Thr Arg Thr Leu Val Ala Ala Arg Ala Phe Val Gln Gly Leu 195 200 205 Glu Thr Gly Arg Asn Val Val Ser Glu Ala Leu Lys Val Pro Val Ser 210 215 220 Glu Gly Cys Ser Gln Ala Leu Met Arg Leu Ile Gly Cys Pro Leu Cys 225 230 235 240 Arg Gly Val Pro Ser Leu Met Pro Cys Gln Gly Phe Cys Leu Asn Val 245 250 255 Val Arg Gly Cys Leu Ser Ser Arg Gly Leu Glu Pro Asp Trp Gly Asn 260 265 270 Tyr Leu Asp Gly Leu Leu Ile Leu Ala Asp Lys Leu Gln Gly Pro Phe 275 280 285 Ser Phe Glu Leu Thr Ala Glu Ser Ile Gly Val Lys Ile Ser Glu Gly 290 295 300 Leu Met Tyr Leu Gln Glu Asn Ser Ala Lys Val Ser Ala Gln Val Phe 305 310 315 320 Gln Glu Cys Gly Pro Pro Asp Pro Val Pro Ala Arg Asn Arg Arg Ala 325 330 335 Pro Pro Pro Arg Glu Glu Ala Gly Arg Leu Trp Ser Met Val Thr Glu 340 345 350 Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Asn Leu His Arg Leu Val 355 360 365 Trp Glu Leu Arg Glu Arg Leu Ala Arg Met Arg Gly Phe Trp Ala Arg 370 375 380 Leu Ser Leu Thr Val Cys Gly Asp Ser Arg Met Ala Ala Asp Ala Ser 385 390 395 400 Leu Glu Ala Ala Pro Cys Trp Thr Gly Ala Gly Arg Gly Arg Tyr Leu 405 410 415 Pro Pro Val Val Gly Gly Ser Pro Ala Glu Gln Val Asn Asn Pro Glu 420 425 430 Leu Asn Val Asp Ala Ser Gly Pro Asp Val Pro Thr Arg Arg Arg Arg 435 440 445 Leu Arg Leu Arg Ala Ala Thr Ala Arg Met Lys Thr Ala Ala Leu Gly 450 455 460 His Asp Leu Asp Gly Gln Asp Ala Asp Glu Asp Ala Ser Gly Ser Gly 465 470 475 480 Gly Gly Gln Gln Tyr Ala Asp Asp Trp Met Ala Gly Ala Val Ala Pro 485 490 495 Pro Ala Arg Pro Pro Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser 500 505 510 Gly Gly Lys Gly Gly Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser 515 520 525 Arg Ser 530 79 1762 DNA Homo sapiens CDS (14)..(1750) 79 caccggatcc acc atg tcc gcg ctg cga cct ctc ctg ctt ctg ctg ctg 49 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu 1 5 10 cct ctg tgt ccc ggt cct ggt ccc gga ccc ggg agc gag gca aag gtc 97 Pro Leu Cys Pro Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val 15 20 25 acc cgg agt tgt gca gag acc cgg cag gtg ctg ggg gcc cgg gga tat 145 Thr Arg Ser Cys Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr 30 35 40 agc tta aac cta atc cct ccc gcc ctg atc tca ggt gag cac ctc cgg 193 Ser Leu Asn Leu Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg 45 50 55 60 gtc tgt ccc cag gag tac acc tgc tgt tcc agt gag aca gag cag agg 241 Val Cys Pro Gln Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg 65 70 75 ctg atc agg gag act gag gcc acc ttc cga ggc ctg gtg gag gac agc 289 Leu Ile Arg Glu Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser 80 85 90 ggc tcc ttt ctg gtt cac aca ctg gct gcc agg cac aga aaa ttt gat 337 Gly Ser Phe Leu Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp 95 100 105 gag ttt ttt ctg gag atg ctc tca gta gcc cag cac tct ctg acc cag 385 Glu Phe Phe Leu Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln 110 115 120 ctc ttc tcc cac tcc tac ggc cgc ctg tat gcc cag cac gcc ctc ata 433 Leu Phe Ser His Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile 125 130 135 140 ttc aat ggc ctg ttc tct cgg ctg cga gac ttc tat ggg gaa tct ggt 481 Phe Asn Gly Leu Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly 145 150 155 gag ggg ttg gat gac acc ctg gcg gat ttc tgg gca cag ctc ctg gag 529 Glu Gly Leu Asp Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu 160 165 170 aga gtg ttc ccg ctg ctg cac cca cag tac agc ttc ccc cct gac tac 577 Arg Val Phe Pro Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr 175 180 185 ctg ctc tgc ctc tca cgc ttg gcc tca tct acc gat ggc tct ctg cag 625 Leu Leu Cys Leu Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln 190 195 200 ccc ttt ggg gac tca ccc cgc cgc ctc cgc ctg cag ata acc cgg acc 673 Pro Phe Gly Asp Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr 205 210 215 220 ctg gtg gct gcc cga gcc ttt gtg cag ggc ctg gag act gga aga aat 721 Leu Val Ala Ala Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn 225 230 235 gtg gtc agc gaa gcg ctt aag gtg ccg gtg tct gaa ggc tgc agc cag 769 Val Val Ser Glu Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln 240 245 250 gct ctg atg cgt ctc atc ggc tgt ccc ctg tgc cgg ggg gtc ccc tca 817 Ala Leu Met Arg Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser 255 260 265 ctt atg ccc tgc cag ggc ttc tgc ctc aac gtg gtt cgt ggc tgt ctc 865 Leu Met Pro Cys Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu 270 275 280 agc agc agg gga ctg gag cct gac tgg ggc aac tat ctg gat ggt ctc 913 Ser Ser Arg Gly Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu 285 290 295 300 ctg atc ctg gct gat aag ctc cag ggc ccc ttt tcc ttt gag ctg acg 961 Leu Ile Leu Ala Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr 305 310 315 gcc gag tcc att ggg gtg aag atc tcg gag ggt ttg atg tac ctg cag 1009 Ala Glu Ser Ile Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln 320 325 330 gaa aac agt gcg aag gtg tcc gcc cag gtg ttt cag gag tgc ggc ccc 1057 Glu Asn Ser Ala Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro 335 340 345 ccc gac ccg gtg cct gcc cgc aac cgt cga gcc ccg ccg ccc cgg gaa 1105 Pro Asp Pro Val Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu 350 355 360 gag gcg ggc cgg ctg tgg tcg atg gtg acc gag gag gag cgg ccc acg 1153 Glu Ala Gly Arg Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr 365 370 375 380 acg gcc gca ggc acc aac ctg cac cgg ctg gtg tgg gag ctc cgc gag 1201 Thr Ala Ala Gly Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu 385 390 395 cgt ctg gcc cgg atg cgg ggc ttc tgg gcc cgg ctg tcc ctg acg gtg 1249 Arg Leu Ala Arg Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val 400 405 410 tgc gga gac tct cgc atg gca gcg gac gcc tcg ctg gag gcg gcg ccc 1297 Cys Gly Asp Ser Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro 415 420 425 tgc tgg acc gga gcc ggg cgg ggc cgg tac ttg ccg cca gtg gtc ggg 1345 Cys Trp Thr Gly Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly 430 435 440 ggc tcc ccg gcc gag cag gtc aac aac ccc gag ctc aag gtg gac gcc 1393 Gly Ser Pro Ala Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala 445 450 455 460 tcg ggc ccc gat gtc ccg aca cgg cgg cgt cgg cta cag ctc cgg gcg 1441 Ser Gly Pro Asp Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala 465 470 475 gcc acg gcc aga atg aaa acg gcc gca ctg gga cac gac ctg gac ggg 1489 Ala Thr Ala Arg Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly 480 485 490 cag gac gcg gat gag gat gcc agc ggc tct gga ggg gga cag cag tat 1537 Gln Asp Ala Asp Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr 495 500 505 gca gat gac tgg atg gct ggg gct gtg gct ccc cca gcc cgg cct cct 1585 Ala Asp Asp Trp Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro 510 515 520 cgg cct cca tac cct cct aga agg gat ggt tct ggg ggc aaa gga gga 1633 Arg Pro Pro Tyr Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly 525 530 535 540 ggt ggc agt gcc cgc tac aac cag ggc cgg agc agg agt ggg ggg gca 1681 Gly Gly Ser Ala Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala 545 550 555 tct att ggt ttt cac acc caa acc atc ctc att ctc tcc ctc tca gcc 1729 Ser Ile Gly Phe His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala 560 565 570 ctg gcc ctg ctt gga cct cga taggtcgacg gc 1762 Leu Ala Leu Leu Gly Pro Arg 575 80 579 PRT Homo sapiens 80 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg 385 390 395 400 Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser 405 410 415 Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly 420 425 430 Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala 435 440 445 Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp 450 455 460 Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg 465 470 475 480 Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp 485 490 495 Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp 500 505 510 Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr 515 520 525 Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala 530 535 540 Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe 545 550 555 560 His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu 565 570 575 Gly Pro Arg 81 1242 DNA Homo sapiens CDS (1)..(1242) 81 atg ggg tcg acc gac tcc aag ctg aac ttc cgg aag gcg gtg atc cag 48 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 ctc acc acc aag acg cag ccc gtg gaa gcc acc gat gat gcc ttt tgg 96 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 gac cag ttc tgg gca gac aca gcc acc tcg gtg cag gat gtg ttt gca 144 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 ctg gtg ccg gca gca gag atc cgg gcc gtg cgg gaa gag tca ccc tcc 192 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 aac ttg gcc acc ctg tgc tac aag gcc gtt gag agg ctg gtg cag gga 240 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 gct gag agt ggc tgc cac tcg gag aag gag aag cag atc gtc ctg aac 288 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 tgc agc cgg ctg ctc acc cgc gtg ctg ccc tac atc ttt gag gac ccc 336 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 gac tgg agg ggc ttc ttc tgg tcc aca gtg ccc ggg gca ggg cga gga 384 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 ggg cag gga gaa gag gat gat gag cat gcc agg ccc ctg gcc gag tcc 432 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 ctg ctc ctg gcc att gct gac ctg ctc ttc tgc ccg gac ttc acg gtt 480 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 cag agc cac cgg agg agc act gtg gac tcg gca gag gac gtc cac tcc 528 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 ctg gac agc tgt gaa tac atc tgg gag gct ggt gtg ggc ttc gct cac 576 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 tcc ccc cag cct aac tac atc cac gat atg aac cgg atg gag ctg ctg 624 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 aaa ctg ctg ctg aca tgc ttc tcc gag gcc atg tac ctg ccc cca gct 672 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 ccg gaa agt ggc agc acc aac cca tgg gtt cag ttc ttt tgt tcc acg 720 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 gag aac aga cat gcc ctg ccc ctc ttc acc tcc ctc ctc aac acc gtg 768 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 tgt gcc tat gac cct gtg ggc tac ggg atc ccc tac aac cac ctg ctc 816 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 ttc tct gac tac cgg gaa ccc ctg gtg gag gag gct gcc cag gtg ctc 864 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 att gtc act ttg gac cac gac agt gcc agc agt gcc agc ccc act gtg 912 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 gac ggc acc acc act ggc acc gcc atg gat gat gcc gat cct cca ggc 960 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 cct gag aac ctg ttt gtg aac tac ctg tcc cgc atc cat cgt gag gag 1008 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 gac ttc cag ttc atc ctc aag ggt ata gcc cgg ctg ctg tcc aac ccc 1056 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 ctg ctc cag acc tac ctg cct aac tcc acc aag aag atc cag ttc cac 1104 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 cag gag ctg cta gtt ctc ttc tgg aag ctc tgc gac ttc aac aag aaa 1152 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 ttc ctc ttc ttc gtg ctg aag agc agc gac gtc cta gac atc ctt gtc 1200 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 ccc atc ctc ttc ttc ctc aac gat gcc cgg gcc gat cag tct 1242 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 82 414 PRT Homo sapiens 82 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 83 1912 DNA Homo sapiens CDS (133)..(1812) 83 cgagggccgg gggcggggcg cgccgcttgt ctcctgcgag agccgcgggg gccgcggagc 60 tggagccgga gctgaagccg gagccgggtt ggagtcttgg gcgggggccg ggccggagcg 120 ggctccagag ac atg ggg tcg acc gac tcc aag ctg aac ttc cgg aag gcg 171 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala 1 5 10 gtg atc cag ctc acc acc aag acg cag ccc gtg gaa gcc acc gat gat 219 Val Ile Gln Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp 15 20 25 gcc tat gac cct gtg ggc tac ggg atc ccc tac aac cac ctg ctc ttc 267 Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu Phe 30 35 40 45 tct gac acc ggg gaa ccc ctg gtg gag gag gct gcc cag gtg ctc att 315 Ser Asp Thr Gly Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu Ile 50 55 60 gtc act ttg gac cac gac agt gcc agc agt gcc agc ccc act gtg gac 363 Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val Asp 65 70 75 ggc acc acc act ggc acc gcc atg gat gat gcc gat cct cca ggc cct 411 Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly Pro 80 85 90 gag aac ctg ttt gtg aac tac ctg tcc cgc atc cat cgt gag gag gac 459 Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu Asp 95 100 105 ttc cag ttc atc ctc aag ggt ata gcc cgg ctg ctg tcc aac ccc ctg 507 Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro Leu 110 115 120 125 ctc cag acc tac ctg cct aac tcc acc aag aag atc cag ttc cac cag 555 Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His Gln 130 135 140 gag ctg cta gtt ctc ttc tgg aag ctc tgc gac ttc aac aag aaa ttc 603 Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys Phe 145 150 155 ctc ttc ttc gtg ctg aag agc agc gac gtc cta gac atc ctt gtc ccc 651 Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val Pro 160 165 170 atc ctc ttc ttc ctc aac gat gcc cgg gcc gat cag tct cgg gtg ggc 699 Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser Arg Val Gly 175 180 185 ctg atg cac att ggt gtc ttc atc ttg ctg ctt ctg agc ggg gag cgg 747 Leu Met His Ile Gly Val Phe Ile Leu Leu Leu Leu Ser Gly Glu Arg 190 195 200 205 aac ttc ggg gtg cgg ctg aac aaa ccc tac tca atc cgc gtg ccc atg 795 Asn Phe Gly Val Arg Leu Asn Lys Pro Tyr Ser Ile Arg Val Pro Met 210 215 220 gac atc cca gtc ttc aca ggg acc cac gcc gac ctg ctc att gtg gtg 843 Asp Ile Pro Val Phe Thr Gly Thr His Ala Asp Leu Leu Ile Val Val 225 230 235 ttc cac aag atc atc acc agc ggg cac cag cgg ttg cag ccc ctc ttc 891 Phe His Lys Ile Ile Thr Ser Gly His Gln Arg Leu Gln Pro Leu Phe 240 245 250 gac tgc ctg ctc acc atc gtg gtc aac gtg tcc ccc tac ctc aag agc 939 Asp Cys Leu Leu Thr Ile Val Val Asn Val Ser Pro Tyr Leu Lys Ser 255 260 265 ctg tcc atg gtg acc gcc aac aag ttg ctg cac ctg ctg gag gcc ttc 987 Leu Ser Met Val Thr Ala Asn Lys Leu Leu His Leu Leu Glu Ala Phe 270 275 280 285 tcc acc acc tgg ttc ctc ttc tct gcc gcc cag aac cac cac ctg gtc 1035 Ser Thr Thr Trp Phe Leu Phe Ser Ala Ala Gln Asn His His Leu Val 290 295 300 ttc ttc ctc ctg gag gtc ttc aac aac atc atc cag tac cag ttt gat 1083 Phe Phe Leu Leu Glu Val Phe Asn Asn Ile Ile Gln Tyr Gln Phe Asp 305 310 315 ggc aac tcc aac ctg gtc tac gcc atc atc cgc aag cgc agc atc ttc 1131 Gly Asn Ser Asn Leu Val Tyr Ala Ile Ile Arg Lys Arg Ser Ile Phe 320 325 330 cac cag ctg gcc aac ctg ccc acg gac ccg ccc acc att cac aag gcc 1179 His Gln Leu Ala Asn Leu Pro Thr Asp Pro Pro Thr Ile His Lys Ala 335 340 345 ctg cag cgg cgc cgg cgg aca cct gag ccc ttg tct cgc acc ggc tcc 1227 Leu Gln Arg Arg Arg Arg Thr Pro Glu Pro Leu Ser Arg Thr Gly Ser 350 355 360 365 cag gag ggc acc tcc atg gag ggc tcc cgc ccc gct gcc cct gca gag 1275 Gln Glu Gly Thr Ser Met Glu Gly Ser Arg Pro Ala Ala Pro Ala Glu 370 375 380 cca ggc acc ctc aag acc agt ctg gtg gct act cca ggc att gac aag 1323 Pro Gly Thr Leu Lys Thr Ser Leu Val Ala Thr Pro Gly Ile Asp Lys 385 390 395 ctg acc gag aag tcc cag gtg tca gag gat ggc acc ttg cgg tcc ctg 1371 Leu Thr Glu Lys Ser Gln Val Ser Glu Asp Gly Thr Leu Arg Ser Leu 400 405 410 gaa cct gag ccc cag cag agc ttg gag gat ggc agc ccg gct aag ggg 1419 Glu Pro Glu Pro Gln Gln Ser Leu Glu Asp Gly Ser Pro Ala Lys Gly 415 420 425 gag ccc agc cag gca tgg agg gag cag cgg cga cca tcc acc tca tca 1467 Glu Pro Ser Gln Ala Trp Arg Glu Gln Arg Arg Pro Ser Thr Ser Ser 430 435 440 445 gcc agt ggg cag tgg agc cca acg cca gag tgg gtc ctc tcc tgg aag 1515 Ala Ser Gly Gln Trp Ser Pro Thr Pro Glu Trp Val Leu Ser Trp Lys 450 455 460 tcg aag ctg ccg ctg cag acc atc atg agg ctg ctg cag gtg ctg gtt 1563 Ser Lys Leu Pro Leu Gln Thr Ile Met Arg Leu Leu Gln Val Leu Val 465 470 475 ccg cag gtg gag aag atc tgc atc gac aag ggc ctg acg gat gag tct 1611 Pro Gln Val Glu Lys Ile Cys Ile Asp Lys Gly Leu Thr Asp Glu Ser 480 485 490 gag atc ctg cgg ttc ctg cag cat ggc acc ctg gtg ggg ctg ctg ccc 1659 Glu Ile Leu Arg Phe Leu Gln His Gly Thr Leu Val Gly Leu Leu Pro 495 500 505 gtg ccc cac ccc atc ctc atc cgc aag tac cag gcc aac tcg ggc act 1707 Val Pro His Pro Ile Leu Ile Arg Lys Tyr Gln Ala Asn Ser Gly Thr 510 515 520 525 gcc atg tgg ttc cgc acc tac atg tgg ggc gtc atc tat ctg agg aat 1755 Ala Met Trp Phe Arg Thr Tyr Met Trp Gly Val Ile Tyr Leu Arg Asn 530 535 540 gtg gac ccc cct gtc tgg tac gac acc gac gtg aag ctg ttt gag ata 1803 Val Asp Pro Pro Val Trp Tyr Asp Thr Asp Val Lys Leu Phe Glu Ile 545 550 555 cag cgg gtg tgaggatgaa gccgacgagg ggctcagtct aggggaaggc 1852 Gln Arg Val 560 agggccttgg tccctgaggc ttcccccatc caccattctg agctttaaat taccacgatc 1912 84 560 PRT Homo sapiens 84 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Tyr Asp 20 25 30 Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu Phe Ser Asp Thr 35 40 45 Gly Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu Ile Val Thr Leu 50 55 60 Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val Asp Gly Thr Thr 65 70 75 80 Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly Pro Glu Asn Leu 85 90 95 Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu Asp Phe Gln Phe 100 105 110 Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro Leu Leu Gln Thr 115 120 125 Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His Gln Glu Leu Leu 130 135 140 Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys Phe Leu Phe Phe 145 150 155 160 Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val Pro Ile Leu Phe 165 170 175 Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser Arg Val Gly Leu Met His 180 185 190 Ile Gly Val Phe Ile Leu Leu Leu Leu Ser Gly Glu Arg Asn Phe Gly 195 200 205 Val Arg Leu Asn Lys Pro Tyr Ser Ile Arg Val Pro Met Asp Ile Pro 210 215 220 Val Phe Thr Gly Thr His Ala Asp Leu Leu Ile Val Val Phe His Lys 225 230 235 240 Ile Ile Thr Ser Gly His Gln Arg Leu Gln Pro Leu Phe Asp Cys Leu 245 250 255 Leu Thr Ile Val Val Asn Val Ser Pro Tyr Leu Lys Ser Leu Ser Met 260 265 270 Val Thr Ala Asn Lys Leu Leu His Leu Leu Glu Ala Phe Ser Thr Thr 275 280 285 Trp Phe Leu Phe Ser Ala Ala Gln Asn His His Leu Val Phe Phe Leu 290 295 300 Leu Glu Val Phe Asn Asn Ile Ile Gln Tyr Gln Phe Asp Gly Asn Ser 305 310 315 320 Asn Leu Val Tyr Ala Ile Ile Arg Lys Arg Ser Ile Phe His Gln Leu 325 330 335 Ala Asn Leu Pro Thr Asp Pro Pro Thr Ile His Lys Ala Leu Gln Arg 340 345 350 Arg Arg Arg Thr Pro Glu Pro Leu Ser Arg Thr Gly Ser Gln Glu Gly 355 360 365 Thr Ser Met Glu Gly Ser Arg Pro Ala Ala Pro Ala Glu Pro Gly Thr 370 375 380 Leu Lys Thr Ser Leu Val Ala Thr Pro Gly Ile Asp Lys Leu Thr Glu 385 390 395 400 Lys Ser Gln Val Ser Glu Asp Gly Thr Leu Arg Ser Leu Glu Pro Glu 405 410 415 Pro Gln Gln Ser Leu Glu Asp Gly Ser Pro Ala Lys Gly Glu Pro Ser 420 425 430 Gln Ala Trp Arg Glu Gln Arg Arg Pro Ser Thr Ser Ser Ala Ser Gly 435 440 445 Gln Trp Ser Pro Thr Pro Glu Trp Val Leu Ser Trp Lys Ser Lys Leu 450 455 460 Pro Leu Gln Thr Ile Met Arg Leu Leu Gln Val Leu Val Pro Gln Val 465 470 475 480 Glu Lys Ile Cys Ile Asp Lys Gly Leu Thr Asp Glu Ser Glu Ile Leu 485 490 495 Arg Phe Leu Gln His Gly Thr Leu Val Gly Leu Leu Pro Val Pro His 500 505 510 Pro Ile Leu Ile Arg Lys Tyr Gln Ala Asn Ser Gly Thr Ala Met Trp 515 520 525 Phe Arg Thr Tyr Met Trp Gly Val Ile Tyr Leu Arg Asn Val Asp Pro 530 535 540 Pro Val Trp Tyr Asp Thr Asp Val Lys Leu Phe Glu Ile Gln Arg Val 545 550 555 560 85 3146 DNA Homo sapiens CDS (1)..(2292) 85 atg ggg tcg acc gac tcc aag ctg aac ttc cgg aag gcg gtg atc cag 48 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 ctc acc acc aag acg cag ccc gtg gaa gcc acc gat gat gcc ttt tgg 96 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 gac cag ttc tgg gca gac aca gcc acc tcg gtg cag gat gtg ttt gca 144 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 ctg gtg ccg gca gca gag atc cgg gcc gtg cgg gaa gag tca ccc tcc 192 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 aac ttg gcc acc ctg tgc tac aag gcc gtt gag aag ctg gtg cag gga 240 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Lys Leu Val Gln Gly 65 70 75 80 gct gag agt ggc tgc cac tcg gag aag gag aag cag atc gtc ctg aac 288 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 tgc agc cgg ctg ctc acc cgc gtg ctg ccc tac atc ttt gag gac ccc 336 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 gac tgg agg ggc ttc ttc tgg tcc aca gtg ccc cag cag gga gaa gag 384 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gln Gln Gly Glu Glu 115 120 125 gat gat gag cat gcc agg ccc ctg gcc gag tcc ctg ctc ctg gcc att 432 Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser Leu Leu Leu Ala Ile 130 135 140 gct gac ctg ctc ttc tgc ccg gac ttc acg gtt cag agc cac cgg agg 480 Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val Gln Ser His Arg Arg 145 150 155 160 agc act gtg gac tcg gca gag gac gtc cac tcc ctg gac agc tgt gaa 528 Ser Thr Val Asp Ser Ala Glu Asp Val His Ser Leu Asp Ser Cys Glu 165 170 175 tac atc tgg gag gct ggt gtg ggc ttc gct cac tcc ccc cag cct aac 576 Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His Ser Pro Gln Pro Asn 180 185 190 tac atc cac gat atg aac cgg atg gag ctg ctg aaa ctg ctg ctg aca 624 Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu Lys Leu Leu Leu Thr 195 200 205 tgc ttc tcc gag gcc atg tac ctg ccc cca gct ccg gaa agt ggc agc 672 Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala Pro Glu Ser Gly Ser 210 215 220 acc aac cca tgg gtt cag ttc ttt tgt tcc acg gag aac aga cat gcc 720 Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr Glu Asn Arg His Ala 225 230 235 240 ctg ccc ctc ttc acc tcc ctc ctc aac acc gtg tgt gcc tat gac cct 768 Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val Cys Ala Tyr Asp Pro 245 250 255 gtg ggc tac ggg atc ccc tac aac cac ctg ctc ttc tct gac tac cgg 816 Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu Phe Ser Asp Tyr Arg 260 265 270 gaa ccc ctg gtg gag gag gct gcc cag gtg ctc att gtc act ttg gac 864 Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu Ile Val Thr Leu Asp 275 280 285 cac gac agt gcc agc agt gcc agc ccc act gtg gac ggc acc acc act 912 His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val Asp Gly Thr Thr Thr 290 295 300 ggc acc gcc atg gat gat gcc gat gac ttc cag ttc atc ctc aag ggt 960 Gly Thr Ala Met Asp Asp Ala Asp Asp Phe Gln Phe Ile Leu Lys Gly 305 310 315 320 ata gcc cgg ctg ctg tcc aac ccc ctg ctc cag acc tac ctg cct aac 1008 Ile Ala Arg Leu Leu Ser Asn Pro Leu Leu Gln Thr Tyr Leu Pro Asn 325 330 335 tcc acc aag aag atc cag ttc cac cag gag ctg cta gtt ctc ttc tgg 1056 Ser Thr Lys Lys Ile Gln Phe His Gln Glu Leu Leu Val Leu Phe Trp 340 345 350 aag ctc tgc gac ttc aac aag aaa ttc ctc ttc ttc gtg ctg aag agc 1104 Lys Leu Cys Asp Phe Asn Lys Lys Phe Leu Phe Phe Val Leu Lys Ser 355 360 365 agc gac gtc cta gac atc ctt gtc ccc atc ctc ttc ttc ctc aac gat 1152 Ser Asp Val Leu Asp Ile Leu Val Pro Ile Leu Phe Phe Leu Asn Asp 370 375 380 gcc cgg gcc gat cag tct cgg gtg ggc ctg atg cac att ggt gtc ttc 1200 Ala Arg Ala Asp Gln Ser Arg Val Gly Leu Met His Ile Gly Val Phe 385 390 395 400 atc ttg ctg ctt ctg agc ggg gag cgg aac ttc ggg gtg cgg ctg aac 1248 Ile Leu Leu Leu Leu Ser Gly Glu Arg Asn Phe Gly Val Arg Leu Asn 405 410 415 aaa ccc tac tca atc cgc gtg ccc atg gac atc cca gtc ttc aca ggg 1296 Lys Pro Tyr Ser Ile Arg Val Pro Met Asp Ile Pro Val Phe Thr Gly 420 425 430 acc cac gcc gac ctg ctc att gtg gtg ttc cac aag atc atc acc agc 1344 Thr His Ala Asp Leu Leu Ile Val Val Phe His Lys Ile Ile Thr Ser 435 440 445 ggg cac cag cgg ttg cag ccc ctc ttc gac tgc ctg ctc acc atc gtg 1392 Gly His Gln Arg Leu Gln Pro Leu Phe Asp Cys Leu Leu Thr Ile Val 450 455 460 gtc aac gtg tcc ccc tac ctc aag agc ctg tcc atg gtg acc gcc aac 1440 Val Asn Val Ser Pro Tyr Leu Lys Ser Leu Ser Met Val Thr Ala Asn 465 470 475 480 aag ttg ctg cac ctg ctg gag gcc ttc tcc acc acc tgg ttc ctc ttc 1488 Lys Leu Leu His Leu Leu Glu Ala Phe Ser Thr Thr Trp Phe Leu Phe 485 490 495 tct gcc gcc cag aac cac cac ctg gtc ttc ttc ctc ctg gag gtc ttc 1536 Ser Ala Ala Gln Asn His His Leu Val Phe Phe Leu Leu Glu Val Phe 500 505 510 aac aac atc atc cag tac cag ttt gat ggc aac tcc aac ctg gtc tac 1584 Asn Asn Ile Ile Gln Tyr Gln Phe Asp Gly Asn Ser Asn Leu Val Tyr 515 520 525 gcc atc atc cgc aag cgc agc atc ttc cac cag ctg gcc aac ctg ccc 1632 Ala Ile Ile Arg Lys Arg Ser Ile Phe His Gln Leu Ala Asn Leu Pro 530 535 540 acg gac ccg ccc acc att cac aag gcc ctg cag cgg cgc cgg cgg aca 1680 Thr Asp Pro Pro Thr Ile His Lys Ala Leu Gln Arg Arg Arg Arg Thr 545 550 555 560 cct gag ccc ttg tct cgc acc ggc tcc cag gag ggc acc tcc atg gag 1728 Pro Glu Pro Leu Ser Arg Thr Gly Ser Gln Glu Gly Thr Ser Met Glu 565 570 575 ggc tcc cgc ccc gct gcc cct gca gag cca ggc acc ctc aag acc agt 1776 Gly Ser Arg Pro Ala Ala Pro Ala Glu Pro Gly Thr Leu Lys Thr Ser 580 585 590 ctg gtg gct act cca ggc att gac aag ctg acc gag aag tcc cag gtg 1824 Leu Val Ala Thr Pro Gly Ile Asp Lys Leu Thr Glu Lys Ser Gln Val 595 600 605 tca gag gat ggc acc ttg cgg tcc ctg gaa cct gag ccc cag cag agc 1872 Ser Glu Asp Gly Thr Leu Arg Ser Leu Glu Pro Glu Pro Gln Gln Ser 610 615 620 ttg gag gat ggc agc ccg gct aag ggg gag ccc agc cag gca tgg agg 1920 Leu Glu Asp Gly Ser Pro Ala Lys Gly Glu Pro Ser Gln Ala Trp Arg 625 630 635 640 gag cag cgg cga ccg tcc acc tca tca gcc agt ggg cag tgg agc cca 1968 Glu Gln Arg Arg Pro Ser Thr Ser Ser Ala Ser Gly Gln Trp Ser Pro 645 650 655 acg cca gag tgg gtc ctc tcc tgg aag tcg aag ctg ccg ctg cag acc 2016 Thr Pro Glu Trp Val Leu Ser Trp Lys Ser Lys Leu Pro Leu Gln Thr 660 665 670 atc atg agg ctg ctg cag gtg ctg gtt ccg cag gtg gag aag atc tgc 2064 Ile Met Arg Leu Leu Gln Val Leu Val Pro Gln Val Glu Lys Ile Cys 675 680 685 atc gac aag ggc ctg acg gat gag tct gag atc ctg cgg ttc ctg cag 2112 Ile Asp Lys Gly Leu Thr Asp Glu Ser Glu Ile Leu Arg Phe Leu Gln 690 695 700 cat ggc acc ctg gtg ggg ctg ctg ccc gtg ccc cac ccc atc ctc atc 2160 His Gly Thr Leu Val Gly Leu Leu Pro Val Pro His Pro Ile Leu Ile 705 710 715 720 cgc aag tac cag gcc aac tcg ggc act gcc atg tgg ttc cgc acc tac 2208 Arg Lys Tyr Gln Ala Asn Ser Gly Thr Ala Met Trp Phe Arg Thr Tyr 725 730 735 atg tgg ggc gtc atc tat ctg agg aat gtg gac ccc cct gtc tgg tac 2256 Met Trp Gly Val Ile Tyr Leu Arg Asn Val Asp Pro Pro Val Trp Tyr 740 745 750 gac acc gac gtg aag ctg ttt gag ata cag cgg gtg tgaggatgaa 2302 Asp Thr Asp Val Lys Leu Phe Glu Ile Gln Arg Val 755 760 gccgacgagg ggctcagtct aggggaaggc agggccttgg tccctgaggc ttcccccatc 2362 caccattctg agctttaaat taccacgatc agggcctgga acaggcagag tggccctgag 2422 tgtcatgccc tagagacccc tgtggccagg acaatgtgaa ctggctcaga tccccctcaa 2482 cccctaggct ggactcacag gagccccatc tctggggcta tgcccccacc agagaccact 2542 gcccccaaca ctcggactcc ctctttaaga cctggctcag tgctggcccc tcagtgccca 2602 cccactcctg tgctacccag ccccagaggc agaagccaaa atgggtcact gtgccctaag 2662 gggtttgacc agggaaccac gggctgtccc ttgaggtgcc tggacagggt aagggggtgc 2722 ttccagcctc ctaacccaaa gccagctgtt ccaggctcca ggggaaaaag gtgtggccag 2782 gctgctcctc gaggaggctg ggagctggcc gactgcaaaa gccagactgg ggcacctccc 2842 gtatccttgg ggcatggtgt ggggtggtga gggtctcctg ctatattctc ctggatccat 2902 ggaaatagcc tggctccctc ttacccagta atgaggggca gggaagggaa ctgggaggca 2962 gccgtttagt cctccctgcc ctgcccactg cctggatggg gcgatgccac ccctcatcct 3022 tcacccagct ctggcctctg ggtcccacca cccagccccc cgtgtcagaa caatctttgc 3082 tctgtacaat cggcctcttt acaataaaac ctcctgctcc aaaaaaaaaa aaaaaaaaaa 3142 aaaa 3146 86 764 PRT Homo sapiens 86 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Lys Leu Val Gln Gly 65 70 75 80 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gln Gln Gly Glu Glu 115 120 125 Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser Leu Leu Leu Ala Ile 130 135 140 Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val Gln Ser His Arg Arg 145 150 155 160 Ser Thr Val Asp Ser Ala Glu Asp Val His Ser Leu Asp Ser Cys Glu 165 170 175 Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His Ser Pro Gln Pro Asn 180 185 190 Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu Lys Leu Leu Leu Thr 195 200 205 Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala Pro Glu Ser Gly Ser 210 215 220 Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr Glu Asn Arg His Ala 225 230 235 240 Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val Cys Ala Tyr Asp Pro 245 250 255 Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu Phe Ser Asp Tyr Arg 260 265 270 Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu Ile Val Thr Leu Asp 275 280 285 His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val Asp Gly Thr Thr Thr 290 295 300 Gly Thr Ala Met Asp Asp Ala Asp Asp Phe Gln Phe Ile Leu Lys Gly 305 310 315 320 Ile Ala Arg Leu Leu Ser Asn Pro Leu Leu Gln Thr Tyr Leu Pro Asn 325 330 335 Ser Thr Lys Lys Ile Gln Phe His Gln Glu Leu Leu Val Leu Phe Trp 340 345 350 Lys Leu Cys Asp Phe Asn Lys Lys Phe Leu Phe Phe Val Leu Lys Ser 355 360 365 Ser Asp Val Leu Asp Ile Leu Val Pro Ile Leu Phe Phe Leu Asn Asp 370 375 380 Ala Arg Ala Asp Gln Ser Arg Val Gly Leu Met His Ile Gly Val Phe 385 390 395 400 Ile Leu Leu Leu Leu Ser Gly Glu Arg Asn Phe Gly Val Arg Leu Asn 405 410 415 Lys Pro Tyr Ser Ile Arg Val Pro Met Asp Ile Pro Val Phe Thr Gly 420 425 430 Thr His Ala Asp Leu Leu Ile Val Val Phe His Lys Ile Ile Thr Ser 435 440 445 Gly His Gln Arg Leu Gln Pro Leu Phe Asp Cys Leu Leu Thr Ile Val 450 455 460 Val Asn Val Ser Pro Tyr Leu Lys Ser Leu Ser Met Val Thr Ala Asn 465 470 475 480 Lys Leu Leu His Leu Leu Glu Ala Phe Ser Thr Thr Trp Phe Leu Phe 485 490 495 Ser Ala Ala Gln Asn His His Leu Val Phe Phe Leu Leu Glu Val Phe 500 505 510 Asn Asn Ile Ile Gln Tyr Gln Phe Asp Gly Asn Ser Asn Leu Val Tyr 515 520 525 Ala Ile Ile Arg Lys Arg Ser Ile Phe His Gln Leu Ala Asn Leu Pro 530 535 540 Thr Asp Pro Pro Thr Ile His Lys Ala Leu Gln Arg Arg Arg Arg Thr 545 550 555 560 Pro Glu Pro Leu Ser Arg Thr Gly Ser Gln Glu Gly Thr Ser Met Glu 565 570 575 Gly Ser Arg Pro Ala Ala Pro Ala Glu Pro Gly Thr Leu Lys Thr Ser 580 585 590 Leu Val Ala Thr Pro Gly Ile Asp Lys Leu Thr Glu Lys Ser Gln Val 595 600 605 Ser Glu Asp Gly Thr Leu Arg Ser Leu Glu Pro Glu Pro Gln Gln Ser 610 615 620 Leu Glu Asp Gly Ser Pro Ala Lys Gly Glu Pro Ser Gln Ala Trp Arg 625 630 635 640 Glu Gln Arg Arg Pro Ser Thr Ser Ser Ala Ser Gly Gln Trp Ser Pro 645 650 655 Thr Pro Glu Trp Val Leu Ser Trp Lys Ser Lys Leu Pro Leu Gln Thr 660 665 670 Ile Met Arg Leu Leu Gln Val Leu Val Pro Gln Val Glu Lys Ile Cys 675 680 685 Ile Asp Lys Gly Leu Thr Asp Glu Ser Glu Ile Leu Arg Phe Leu Gln 690 695 700 His Gly Thr Leu Val Gly Leu Leu Pro Val Pro His Pro Ile Leu Ile 705 710 715 720 Arg Lys Tyr Gln Ala Asn Ser Gly Thr Ala Met Trp Phe Arg Thr Tyr 725 730 735 Met Trp Gly Val Ile Tyr Leu Arg Asn Val Asp Pro Pro Val Trp Tyr 740 745 750 Asp Thr Asp Val Lys Leu Phe Glu Ile Gln Arg Val 755 760 87 3314 DNA Homo sapiens CDS (97)..(2460) 87 gcgagagccg cgggggccgc ggagctggag ccggagctga agccggagcc gggttggagt 60 ctgggcgggg gccgggccgg agcgggctcc agagac atg ggg tcg acc gac tcc 114 Met Gly Ser Thr Asp Ser 1 5 aag ctg aac ttc cgg aag gcg gtg atc cag ctc acc acc aag acg cag 162 Lys Leu Asn Phe Arg Lys Ala Val Ile Gln Leu Thr Thr Lys Thr Gln 10 15 20 ccc gtg gaa gcc acc gat gat gcc ttt tgg gac cag ttc tgg gca gac 210 Pro Val Glu Ala Thr Asp Asp Ala Phe Trp Asp Gln Phe Trp Ala Asp 25 30 35 aca gcc acc tcg gtg cag gat gtg ttt gca ctg gtg ccg gca gca gag 258 Thr Ala Thr Ser Val Gln Asp Val Phe Ala Leu Val Pro Ala Ala Glu 40 45 50 atc cgg gcc gtg cgg gaa gag tca ccc tcc aac ttg gcc acc ctg tgc 306 Ile Arg Ala Val Arg Glu Glu Ser Pro Ser Asn Leu Ala Thr Leu Cys 55 60 65 70 tac aag gcc gtt gag aag ctg gtg cag gga gct gag agt ggc tgc cac 354 Tyr Lys Ala Val Glu Lys Leu Val Gln Gly Ala Glu Ser Gly Cys His 75 80 85 tcg gag aag gag aag cag atc gtc ctg aac tgc agc cgg ctg ctc acc 402 Ser Glu Lys Glu Lys Gln Ile Val Leu Asn Cys Ser Arg Leu Leu Thr 90 95 100 cgc gtg ctg ccc tac atc ttt gag gac ccc gac tgg agg ggc ttc ttc 450 Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro Asp Trp Arg Gly Phe Phe 105 110 115 tgg tcc aca gtg ccc ggg gca ggg cga gga ggg cag gga gaa gag gat 498 Trp Ser Thr Val Pro Gly Ala Gly Arg Gly Gly Gln Gly Glu Glu Asp 120 125 130 gat gag cat gcc agg ccc ctg gcc gag tcc ctg ctc ctg gcc att gct 546 Asp Glu His Ala Arg Pro Leu Ala Glu Ser Leu Leu Leu Ala Ile Ala 135 140 145 150 gac ctg ctc ttc tgc ccg gac ttc acg gtt cag agc cac cgg agg agc 594 Asp Leu Leu Phe Cys Pro Asp Phe Thr Val Gln Ser His Arg Arg Ser 155 160 165 act gtg gac tcg gca gag gac gtc cac tcc ctg gac agc tgt gaa tac 642 Thr Val Asp Ser Ala Glu Asp Val His Ser Leu Asp Ser Cys Glu Tyr 170 175 180 atc tgg gag gct ggt gtg ggc ttc gct cac tcc ccc cag cct aac tac 690 Ile Trp Glu Ala Gly Val Gly Phe Ala His Ser Pro Gln Pro Asn Tyr 185 190 195 atc cac gat atg aac cgg atg gag ctg ctg aaa ctg ctg ctg aca tgc 738 Ile His Asp Met Asn Arg Met Glu Leu Leu Lys Leu Leu Leu Thr Cys 200 205 210 ttc tcc gag gcc atg tac ctg ccc cca gct ccg gaa agt ggc agc acc 786 Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala Pro Glu Ser Gly Ser Thr 215 220 225 230 aac cca tgg gtt cag ttc ttt tgt tcc acg gag aac aga cat gcc ctg 834 Asn Pro Trp Val Gln Phe Phe Cys Ser Thr Glu Asn Arg His Ala Leu 235 240 245 ccc ctc ttc acc tcc ctc ctc aac acc gtg tgt gcc tat gac cct gtg 882 Pro Leu Phe Thr Ser Leu Leu Asn Thr Val Cys Ala Tyr Asp Pro Val 250 255 260 ggc tac ggg atc ccc tac aac cac ctg ctc ttc tct gac acc ggg gaa 930 Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu Phe Ser Asp Thr Gly Glu 265 270 275 ccc ctg gtg gag gag gct gcc cag gtg ctc att gtc act ttg gac cac 978 Pro Leu Val Glu Glu Ala Ala Gln Val Leu Ile Val Thr Leu Asp His 280 285 290 gac agt gcc agc agt gcc agc ccc act gtg gac ggc acc acc act ggc 1026 Asp Ser Ala Ser Ser Ala Ser Pro Thr Val Asp Gly Thr Thr Thr Gly 295 300 305 310 acc gcc atg gat gat gcc gat cct cca ggc cct gag aac ctg ttt gtg 1074 Thr Ala Met Asp Asp Ala Asp Pro Pro Gly Pro Glu Asn Leu Phe Val 315 320 325 aac tac ctg tcc cgc atc cat cgt gag gag gac ttc cag ttc atc ctc 1122 Asn Tyr Leu Ser Arg Ile His Arg Glu Glu Asp Phe Gln Phe Ile Leu 330 335 340 aag ggt ata gcc cgg ctg ctg tcc aac ccc ctg ctc cag acc tac ctg 1170 Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro Leu Leu Gln Thr Tyr Leu 345 350 355 cct aac tcc acc aag aag atc cag ttc cac cag gag ctg cta gtt ctc 1218 Pro Asn Ser Thr Lys Lys Ile Gln Phe His Gln Glu Leu Leu Val Leu 360 365 370 ttc tgg aag ctc tgc gac ttc aac aag aaa ttc ctc ttc ttc gtg ctg 1266 Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys Phe Leu Phe Phe Val Leu 375 380 385 390 aag agc agc gac gtc cta gac atc ctt gtc ccc atc ctc ttc ttc ctc 1314 Lys Ser Ser Asp Val Leu Asp Ile Leu Val Pro Ile Leu Phe Phe Leu 395 400 405 aac gat gcc cgg gcc gat cag tct cgg gtg ggc ctg atg cac att ggt 1362 Asn Asp Ala Arg Ala Asp Gln Ser Arg Val Gly Leu Met His Ile Gly 410 415 420 gtc ttc atc ttg ctg ctt ctg agc ggg gag cgg aac ttc ggg gtg cgg 1410 Val Phe Ile Leu Leu Leu Leu Ser Gly Glu Arg Asn Phe Gly Val Arg 425 430 435 ctg aac aaa ccc tac tca atc cgc gtg ccc atg gac atc cca gtc ttc 1458 Leu Asn Lys Pro Tyr Ser Ile Arg Val Pro Met Asp Ile Pro Val Phe 440 445 450 aca ggg acc cac gcc gac ctg ctc att gtg gtg ttc cac aag atc atc 1506 Thr Gly Thr His Ala Asp Leu Leu Ile Val Val Phe His Lys Ile Ile 455 460 465 470 acc agc ggg cac cag cgg ttg cag ccc ctc ttc gac tgc ctg ctc acc 1554 Thr Ser Gly His Gln Arg Leu Gln Pro Leu Phe Asp Cys Leu Leu Thr 475 480 485 atc gtg gtc aac gtg tcc ccc tac ctc aag agc ctg tcc atg gtg acc 1602 Ile Val Val Asn Val Ser Pro Tyr Leu Lys Ser Leu Ser Met Val Thr 490 495 500 gcc aac aag ttg ctg cac ctg ctg gag gcc ttc tcc acc acc tgg ttc 1650 Ala Asn Lys Leu Leu His Leu Leu Glu Ala Phe Ser Thr Thr Trp Phe 505 510 515 ctc ttc tct gcc gcc cag aac cac cac ctg gtc ttc ttc ctc ctg gag 1698 Leu Phe Ser Ala Ala Gln Asn His His Leu Val Phe Phe Leu Leu Glu 520 525 530 gtc ttc aac aac atc atc cag tac cag ttt gat ggc aac tcc aac ctg 1746 Val Phe Asn Asn Ile Ile Gln Tyr Gln Phe Asp Gly Asn Ser Asn Leu 535 540 545 550 gtc tac gcc atc atc cgc aag cgc agc atc ttc cac cag ctg gcc aac 1794 Val Tyr Ala Ile Ile Arg Lys Arg Ser Ile Phe His Gln Leu Ala Asn 555 560 565 ctg ccc acg gac ccg ccc acc att cac aag gcc ctg cag cgg cgc cgg 1842 Leu Pro Thr Asp Pro Pro Thr Ile His Lys Ala Leu Gln Arg Arg Arg 570 575 580 cgg aca cct gag ccc ttg tct cgc acc ggc tcc cag gag ggc acc tcc 1890 Arg Thr Pro Glu Pro Leu Ser Arg Thr Gly Ser Gln Glu Gly Thr Ser 585 590 595 atg gag ggc tcc cgc ccc gct gcc cct gca gag cca ggc acc ctc aag 1938 Met Glu Gly Ser Arg Pro Ala Ala Pro Ala Glu Pro Gly Thr Leu Lys 600 605 610 acc agt ctg gtg gct act cca ggc att gac aag ctg acc gag aag tcc 1986 Thr Ser Leu Val Ala Thr Pro Gly Ile Asp Lys Leu Thr Glu Lys Ser 615 620 625 630 cag gtg tca gag gat ggc acc ttg cgg tcc ctg gaa cct gag ccc cag 2034 Gln Val Ser Glu Asp Gly Thr Leu Arg Ser Leu Glu Pro Glu Pro Gln 635 640 645 cag agc ttg gag gat ggc agc ccg gct aag ggg gag ccc agc cag gca 2082 Gln Ser Leu Glu Asp Gly Ser Pro Ala Lys Gly Glu Pro Ser Gln Ala 650 655 660 tgg agg gag cag cgg cga cca tcc acc tca tca gcc agt ggg cag tgg 2130 Trp Arg Glu Gln Arg Arg Pro Ser Thr Ser Ser Ala Ser Gly Gln Trp 665 670 675 agc cca acg cca gag tgg gtc ctc tcc tgg aag tcg aag ctg ccg ctg 2178 Ser Pro Thr Pro Glu Trp Val Leu Ser Trp Lys Ser Lys Leu Pro Leu 680 685 690 cag acc atc atg agg ctg ctg cag gtg ctg gtt ccg cag gtg gag aag 2226 Gln Thr Ile Met Arg Leu Leu Gln Val Leu Val Pro Gln Val Glu Lys 695 700 705 710 atc tgc atc gac aag ggc ctg acg gat gag tct gag atc ctg cgg ttc 2274 Ile Cys Ile Asp Lys Gly Leu Thr Asp Glu Ser Glu Ile Leu Arg Phe 715 720 725 ctg cag cat ggc acc ctg gtg ggg ctg ctg ccc gtg ccc cac ccc atc 2322 Leu Gln His Gly Thr Leu Val Gly Leu Leu Pro Val Pro His Pro Ile 730 735 740 ctc atc cgc aag tac cag gcc aac tcg ggc act gcc atg tgg ttc cgc 2370 Leu Ile Arg Lys Tyr Gln Ala Asn Ser Gly Thr Ala Met Trp Phe Arg 745 750 755 acc tac atg tgg ggc gtc atc tat ctg agg aat gtg gac ccc cct gtc 2418 Thr Tyr Met Trp Gly Val Ile Tyr Leu Arg Asn Val Asp Pro Pro Val 760 765 770 tgg tac gac acc gac gtg aag ctg ttt gag ata cag cgg gtg 2460 Trp Tyr Asp Thr Asp Val Lys Leu Phe Glu Ile Gln Arg Val 775 780 785 tgaggatgaa gccgacgagg ggctcagtct aggggaaggc agggccttgg tccctgaggc 2520 ttcccccatc caccattctg agctttaaat taccacgatc agggcctgga acaggcagag 2580 tggccctgag tgtcatgccc tagagacccc tgtggccagg acaatgtgaa ctggctcaga 2640 tccccctcaa cccctaggct ggactcacag gagccccatc tctggggcta tgcccccacc 2700 agagaccact gcccccaaca ctcggactcc ctctttaaga cctggctcag tgctggcccc 2760 tcagtgccca cccactcctg tgctacccag ccccagaggc agaagccaaa atgggtcact 2820 gtgccctaag gggtttgacc agggaaccac gggctgtccc ttgaggtgcc tggacagggt 2880 aagggggtgc ttccagcctc ctaacccaaa gccagctgtt ccaggctcca ggggaaaaag 2940 gtgtggccag gctgctcctc gaggaggctg ggagctggcc gactgcaaaa gccagactgg 3000 ggcacctccc gtatccttgg ggcatggtgt ggggtggtga gggtctcctg ctatattctc 3060 ctggatccat ggaaatagcc tggctccctc ttacccagta atgaggggca gggaagggaa 3120 ctgggaggca gccgtttagt cctccctgcc ctgcccactg cctggatggg gcgatgccac 3180 ccctcatcct tcacccagct ctggcctctg ggtcccacca cccagccccc cgtgtcagaa 3240 caatctttgc tctgtacaat cggcctcttt acaataaaac ctcctgctcc aaaaaaaaaa 3300 aaaaaaaaaa aaaa 3314 88 788 PRT Homo sapiens 88 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Lys Leu Val Gln Gly 65 70 75 80 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 Phe Ser Asp Thr Gly Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser Arg Val 405 410 415 Gly Leu Met His Ile Gly Val Phe Ile Leu Leu Leu Leu Ser Gly Glu 420 425 430 Arg Asn Phe Gly Val Arg Leu Asn Lys Pro Tyr Ser Ile Arg Val Pro 435 440 445 Met Asp Ile Pro Val Phe Thr Gly Thr His Ala Asp Leu Leu Ile Val 450 455 460 Val Phe His Lys Ile Ile Thr Ser Gly His Gln Arg Leu Gln Pro Leu 465 470 475 480 Phe Asp Cys Leu Leu Thr Ile Val Val Asn Val Ser Pro Tyr Leu Lys 485 490 495 Ser Leu Ser Met Val Thr Ala Asn Lys Leu Leu His Leu Leu Glu Ala 500 505 510 Phe Ser Thr Thr Trp Phe Leu Phe Ser Ala Ala Gln Asn His His Leu 515 520 525 Val Phe Phe Leu Leu Glu Val Phe Asn Asn Ile Ile Gln Tyr Gln Phe 530 535 540 Asp Gly Asn Ser Asn Leu Val Tyr Ala Ile Ile Arg Lys Arg Ser Ile 545 550 555 560 Phe His Gln Leu Ala Asn Leu Pro Thr Asp Pro Pro Thr Ile His Lys 565 570 575 Ala Leu Gln Arg Arg Arg Arg Thr Pro Glu Pro Leu Ser Arg Thr Gly 580 585 590 Ser Gln Glu Gly Thr Ser Met Glu Gly Ser Arg Pro Ala Ala Pro Ala 595 600 605 Glu Pro Gly Thr Leu Lys Thr Ser Leu Val Ala Thr Pro Gly Ile Asp 610 615 620 Lys Leu Thr Glu Lys Ser Gln Val Ser Glu Asp Gly Thr Leu Arg Ser 625 630 635 640 Leu Glu Pro Glu Pro Gln Gln Ser Leu Glu Asp Gly Ser Pro Ala Lys 645 650 655 Gly Glu Pro Ser Gln Ala Trp Arg Glu Gln Arg Arg Pro Ser Thr Ser 660 665 670 Ser Ala Ser Gly Gln Trp Ser Pro Thr Pro Glu Trp Val Leu Ser Trp 675 680 685 Lys Ser Lys Leu Pro Leu Gln Thr Ile Met Arg Leu Leu Gln Val Leu 690 695 700 Val Pro Gln Val Glu Lys Ile Cys Ile Asp Lys Gly Leu Thr Asp Glu 705 710 715 720 Ser Glu Ile Leu Arg Phe Leu Gln His Gly Thr Leu Val Gly Leu Leu 725 730 735 Pro Val Pro His Pro Ile Leu Ile Arg Lys Tyr Gln Ala Asn Ser Gly 740 745 750 Thr Ala Met Trp Phe Arg Thr Tyr Met Trp Gly Val Ile Tyr Leu Arg 755 760 765 Asn Val Asp Pro Pro Val Trp Tyr Asp Thr Asp Val Lys Leu Phe Glu 770 775 780 Ile Gln Arg Val 785 89 1242 DNA Homo sapiens CDS (1)..(1242) 89 atg ggg tcg acc gac tcc aag ctg aac ttc cgg aag gcg gtg atc cag 48 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 ctc acc acc aag acg cag ccc gtg gaa gcc acc gat gat gcc ttt tgg 96 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 gac cag ttc tgg gca gac aca gcc acc tcg gtg cag gat gtg ttt gca 144 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 ctg gtg ccg gca gca gag atc cgg gcc gtg cgg gaa gag tca ccc tcc 192 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 aac ttg gcc acc ctg tgc tac aag gcc gtt gag agg ctg gtg cag gga 240 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 gct gag agt ggc tgc cac tcg gag aag gag aag cag atc gtc ctg aac 288 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 tgc agc cgg ctg ctc acc cgc gtg ctg ccc tac atc ttt gag gac ccc 336 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 gac tgg agg ggc ttc ttc tgg tcc aca gtg ccc ggg gca ggg cga gga 384 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 ggg cag gga gaa gag gat gat gag cat gcc agg ccc ctg gcc gag tcc 432 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 ctg ctc ctg gcc att gct gac ctg ctc ttc tgc ccg gac ttc acg gtt 480 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 cag agc cac cgg agg agc act gtg gac tcg gca gag gac gtc cac tcc 528 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 ctg gac agc tgt gaa tac atc tgg gag gct ggt gtg ggc ttc gct cac 576 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 tcc ccc cag cct aac tac atc cac gat atg aac cgg atg gag ctg ctg 624 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 aaa ctg ctg ctg aca tgc ttc tcc gag gcc atg tac ctg ccc cca gct 672 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 ccg gaa agt ggc agc acc aac cca tgg gtt cag ttc ttt tgt tcc acg 720 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 gag aac aga cat gcc ctg ccc ctc ttc acc tcc ctc ctc aac acc gtg 768 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 tgt gcc tat gac cct gtg ggc tac ggg atc ccc tac aac cac ctg ctc 816 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 ttc tct gac tac cgg gaa ccc ctg gtg gag gag gct gcc cag gtg ctc 864 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 att gtc act ttg gac cac gac agt gcc agc agt gcc agc ccc act gtg 912 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 gac ggc acc acc act ggc acc gcc atg gat gat gcc gat cct cca ggc 960 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 cct gag aac ctg ttt gtg aac tac ctg tcc cgc atc cat cgt gag gag 1008 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 gac ttc cag ttc atc ctc aag ggt ata gcc cgg ctg ctg tcc aac ccc 1056 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 ctg ctc cag acc tac ctg cct aac tcc acc aag aag atc cag ttc cac 1104 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 cag gag ctg cta gtt ctc ttc tgg aag ctc tgc gac ttc aac aag aaa 1152 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 ttc ctc ttc ttc gtg ctg aag agc agc gac gtc cta gac atc ctt gtc 1200 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 ccc atc ctc ttc ttc ctc aac gat gcc cgg gcc gat cag tct 1242 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 90 414 PRT Homo sapiens 90 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 91 1242 DNA Homo sapiens CDS (1)..(1242) 91 atg ggg tcg acc gac tcc aag ctg aac ttc cgg aag gcg gtg atc cag 48 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 ctc acc acc aag acg cag ccc gtg gaa gcc acc gat gat gcc ttt tgg 96 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 gac cag ttc tgg gca gac aca gcc acc tcg gtg cag gat gtg ttt gca 144 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 ctg gtg ccg gca gca gag atc cgg gcc gtg cgg gaa gag tca ccc tcc 192 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 aac ttg gcc acc ctg tgc tac aag gcc gtt gag agg ctg gtg cag gga 240 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 gct gag agt ggc tgc cac tcg gag aag gag aag cag atc gtc ctg aac 288 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 tgc agc cgg ctg ctc acc cgc gtg ctg ccc tac atc ttt gag gac ccc 336 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 gac tgg agg ggc ttc ttc tgg tcc aca gtg ccc ggg gca ggg cga gga 384 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 ggg cag gga gaa gag gat gat gag cat gcc agg ccc ctg gcc gag tcc 432 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 ctg ctc ctg gcc att gct gac ctg ctc ttc tgc ccg gac ttc acg gtt 480 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 cag agc cac cgg agg agc act gtg gac tcg gca gag gac gtc cac tcc 528 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 ctg gac agc tgt gaa tac atc tgg gag gct ggt gtg ggc ttc gct cac 576 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 tcc ccc cag cct aac tac atc cac gat atg aac cgg atg gag ctg ctg 624 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 aaa ctg ctg ctg aca tgc ttc tcc gag gcc atg tac ctg ccc cca gct 672 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 ccg gaa agt ggc agc acc aac cca tgg gtt cag ttc ttt tgt tcc acg 720 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 gag aac aga cat gcc ctg ccc ctc ttc acc tcc ctc ctc aac acc gtg 768 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 tgt gcc tat gac cct gtg ggc tac ggg atc ccc tac aac cac ctg ctc 816 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 ttc tct gac tac cgg gaa ccc ctg gtg gag gag gct gcc cag gtg ctc 864 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 att gtc act ttg gac cac gac agt gcc agc agt gcc agc ccc act gtg 912 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 gac ggc acc acc act ggc acc gcc atg gat gat gcc gat cct cca ggc 960 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 cct gag aac ctg ttt gtg aac tac ctg tcc cgc atc cat cgt gag gag 1008 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 gac ttc cag ttc atc ctc aag ggt ata gcc cgg ctg ctg tcc aac ccc 1056 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 ctg ctc cag acc tac ctg cct aac tcc acc aag aag atc cag ttc cac 1104 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 cag gag ctg cta gtt ctc ttc tgg aag ctc tgc gac ttc aac aag aaa 1152 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 ttc ctc ttc ttc gtg ctg aag agc agc gac gtc cta gac atc ctt gtc 1200 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 ccc atc ctc ttc ttc ctc aac gat gcc cgg gcc gat cag tct 1242 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 92 414 PRT Homo sapiens 92 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 93 1242 DNA Homo sapiens CDS (1)..(1242) 93 atg ggg tcg acc gac tcc aag ctg aac ttc cgg aag gcg gtg atc cag 48 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 ctc acc acc aag acg cag ccc gtg gaa gcc acc gat gat gcc ttt tgg 96 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 gac cag ttc tgg gca gac aca gcc acc tcg gtg cag gat gtg ttt gca 144 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 ctg gtg ccg gca gca gag atc cgg gcc gtg cgg gaa gag tca ccc tcc 192 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 aac ttg gcc acc ctg tgc tac aag gcc gtt gag agg ctg gtg cag gga 240 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 gct gag agt ggc tgc cac tcg gag aag gag aag cag atc gtc ctg aac 288 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 tgc agc cgg ctg ctc acc cgc gtg ctg ccc tac atc ttt gag gac ccc 336 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 gac tgg agg ggc ttc ttc tgg tcc aca gtg ccc ggg gca ggg cga gga 384 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 ggg cag gga gaa gag gat gat gag cat gcc agg ccc ctg gcc gag tcc 432 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 ctg ctc ctg gcc att gct gac ctg ctc ttc tgc ccg gac ttc acg gtt 480 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 cag agc cac cgg agg agc act gtg gac tcg gca gag gac gtc cac tcc 528 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 ctg gac agc tgt gaa tac atc tgg gag gct ggt gtg ggc ttc gct cac 576 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 tcc ccc cag cct aac tac atc cac gat atg aac cgg atg gag ctg ctg 624 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 aaa ctg ctg ctg aca tgc ttc tcc gag gcc atg tac ctg ccc cca gct 672 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 ccg gaa agt ggc agc acc aac cca tgg gtt cag ttc ttt tgt tcc acg 720 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 gag aac aga cat gcc ctg ccc ctc ttc acc tcc ctc ctc aac acc gtg 768 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 tgt gcc tat gac cct gtg ggc tac ggg atc ccc tac aac cac ctg ctc 816 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 ttc tct gac tac cgg gaa ccc ctg gtg gag gag gct gcc cag gtg ctc 864 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 att gtc act ttg gac cac gac agt gcc agc agt gcc agc ccc act gtg 912 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 gac ggc acc acc act ggc acc gcc atg gat gat gcc gat cct cca ggc 960 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 cct gag aac ctg ttt gtg aac tac ctg tcc cgc atc cat cgt gag gag 1008 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 gac ttc cag ttc atc ctc aag ggt ata gcc cgg ctg ctg tcc aac ccc 1056 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 ctg ctc cag acc tac ctg cct aac tcc acc aag aag atc cag ttc cac 1104 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 cag gag ctg cta gtt ctc ttc tgg aag ctc tgc gac ttc aac aag aaa 1152 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 ttc ctc ttc ttc gtg ctg aag agc agc gac gtc cta gac atc ctt gtc 1200 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 ccc atc ctc ttc ttc ctc aac gat gcc cgg gcc gat cag tct 1242 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 94 414 PRT Homo sapiens 94 Met Gly Ser Thr Asp Ser Lys Leu Asn Phe Arg Lys Ala Val Ile Gln 1 5 10 15 Leu Thr Thr Lys Thr Gln Pro Val Glu Ala Thr Asp Asp Ala Phe Trp 20 25 30 Asp Gln Phe Trp Ala Asp Thr Ala Thr Ser Val Gln Asp Val Phe Ala 35 40 45 Leu Val Pro Ala Ala Glu Ile Arg Ala Val Arg Glu Glu Ser Pro Ser 50 55 60 Asn Leu Ala Thr Leu Cys Tyr Lys Ala Val Glu Arg Leu Val Gln Gly 65 70 75 80 Ala Glu Ser Gly Cys His Ser Glu Lys Glu Lys Gln Ile Val Leu Asn 85 90 95 Cys Ser Arg Leu Leu Thr Arg Val Leu Pro Tyr Ile Phe Glu Asp Pro 100 105 110 Asp Trp Arg Gly Phe Phe Trp Ser Thr Val Pro Gly Ala Gly Arg Gly 115 120 125 Gly Gln Gly Glu Glu Asp Asp Glu His Ala Arg Pro Leu Ala Glu Ser 130 135 140 Leu Leu Leu Ala Ile Ala Asp Leu Leu Phe Cys Pro Asp Phe Thr Val 145 150 155 160 Gln Ser His Arg Arg Ser Thr Val Asp Ser Ala Glu Asp Val His Ser 165 170 175 Leu Asp Ser Cys Glu Tyr Ile Trp Glu Ala Gly Val Gly Phe Ala His 180 185 190 Ser Pro Gln Pro Asn Tyr Ile His Asp Met Asn Arg Met Glu Leu Leu 195 200 205 Lys Leu Leu Leu Thr Cys Phe Ser Glu Ala Met Tyr Leu Pro Pro Ala 210 215 220 Pro Glu Ser Gly Ser Thr Asn Pro Trp Val Gln Phe Phe Cys Ser Thr 225 230 235 240 Glu Asn Arg His Ala Leu Pro Leu Phe Thr Ser Leu Leu Asn Thr Val 245 250 255 Cys Ala Tyr Asp Pro Val Gly Tyr Gly Ile Pro Tyr Asn His Leu Leu 260 265 270 Phe Ser Asp Tyr Arg Glu Pro Leu Val Glu Glu Ala Ala Gln Val Leu 275 280 285 Ile Val Thr Leu Asp His Asp Ser Ala Ser Ser Ala Ser Pro Thr Val 290 295 300 Asp Gly Thr Thr Thr Gly Thr Ala Met Asp Asp Ala Asp Pro Pro Gly 305 310 315 320 Pro Glu Asn Leu Phe Val Asn Tyr Leu Ser Arg Ile His Arg Glu Glu 325 330 335 Asp Phe Gln Phe Ile Leu Lys Gly Ile Ala Arg Leu Leu Ser Asn Pro 340 345 350 Leu Leu Gln Thr Tyr Leu Pro Asn Ser Thr Lys Lys Ile Gln Phe His 355 360 365 Gln Glu Leu Leu Val Leu Phe Trp Lys Leu Cys Asp Phe Asn Lys Lys 370 375 380 Phe Leu Phe Phe Val Leu Lys Ser Ser Asp Val Leu Asp Ile Leu Val 385 390 395 400 Pro Ile Leu Phe Phe Leu Asn Asp Ala Arg Ala Asp Gln Ser 405 410 95 752 DNA Homo sapiens CDS (3)..(731) 95 ct ctg gcc ctc acc ctc atc ttg atg gca gcc tct ggt gct gcg tgc 47 Leu Ala Leu Thr Leu Ile Leu Met Ala Ala Ser Gly Ala Ala Cys 1 5 10 15 gaa gtg agg gac gtt tgt gtt gga agc cct ggt atc ccc ggc act cct 95 Glu Val Arg Asp Val Cys Val Gly Ser Pro Gly Ile Pro Gly Thr Pro 20 25 30 gga tcc cac ggc ctg cca ggc agg gac ggg aga gat ggt gtc aaa gga 143 Gly Ser His Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Val Lys Gly 35 40 45 gac cct ggc cct cca ggc ccc atg ggt ccg cct gga gaa aca cca tgt 191 Asp Pro Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Glu Thr Pro Cys 50 55 60 cct cct ggg aat aat ggg ctg cct gga gcc cct ggt gtc cct gga gag 239 Pro Pro Gly Asn Asn Gly Leu Pro Gly Ala Pro Gly Val Pro Gly Glu 65 70 75 cgt gga gag aag ggg gag cct ggc gag aga ggc cct cca ggg ctt cca 287 Arg Gly Glu Lys Gly Glu Pro Gly Glu Arg Gly Pro Pro Gly Leu Pro 80 85 90 95 gct cat cta gat gag gag ctc caa gcc aca ctc cac gac ttc aga cat 335 Ala His Leu Asp Glu Glu Leu Gln Ala Thr Leu His Asp Phe Arg His 100 105 110 caa atc ctg cag aca agg gga gcc ctc agt ctg cag ggc tcc ata atg 383 Gln Ile Leu Gln Thr Arg Gly Ala Leu Ser Leu Gln Gly Ser Ile Met 115 120 125 aca gta gga gag aag gtc ttc tcc agc aat ggg cag tcc atc act ttt 431 Thr Val Gly Glu Lys Val Phe Ser Ser Asn Gly Gln Ser Ile Thr Phe 130 135 140 gat gcc att cag gag gca tgt gcc aga gca ggc ggc cgc att gct gtc 479 Asp Ala Ile Gln Glu Ala Cys Ala Arg Ala Gly Gly Arg Ile Ala Val 145 150 155 cca agg aat cca gag gaa aat gag gcc att gca agc ttc gtg aag aag 527 Pro Arg Asn Pro Glu Glu Asn Glu Ala Ile Ala Ser Phe Val Lys Lys 160 165 170 175 tac aac aca tat gcc tat gta ggc ctg act gag ggt ccc agc cct gga 575 Tyr Asn Thr Tyr Ala Tyr Val Gly Leu Thr Glu Gly Pro Ser Pro Gly 180 185 190 gac ttc cgc tac tca gat ggg acc cct gta aac tac acc aac tgg tac 623 Asp Phe Arg Tyr Ser Asp Gly Thr Pro Val Asn Tyr Thr Asn Trp Tyr 195 200 205 cga ggg gag cct gca ggt cgg gga aaa gag aag tgt gtg gag atg tac 671 Arg Gly Glu Pro Ala Gly Arg Gly Lys Glu Lys Cys Val Glu Met Tyr 210 215 220 aca gat ggg cag tgg aat gac agg aac tgc ctg tac tcc cga ctg acc 719 Thr Asp Gly Gln Trp Asn Asp Arg Asn Cys Leu Tyr Ser Arg Leu Thr 225 230 235 atc tgt gag ttc tgagaggcat ttaggccatg g 752 Ile Cys Glu Phe 240 96 243 PRT Homo sapiens 96 Leu Ala Leu Thr Leu Ile Leu Met Ala Ala Ser Gly Ala Ala Cys Glu 1 5 10 15 Val Arg Asp Val Cys Val Gly Ser Pro Gly Ile Pro Gly Thr Pro Gly 20 25 30 Ser His Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Val Lys Gly Asp 35 40 45 Pro Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Glu Thr Pro Cys Pro 50 55 60 Pro Gly Asn Asn Gly Leu Pro Gly Ala Pro Gly Val Pro Gly Glu Arg 65 70 75 80 Gly Glu Lys Gly Glu Pro Gly Glu Arg Gly Pro Pro Gly Leu Pro Ala 85 90 95 His Leu Asp Glu Glu Leu Gln Ala Thr Leu His Asp Phe Arg His Gln 100 105 110 Ile Leu Gln Thr Arg Gly Ala Leu Ser Leu Gln Gly Ser Ile Met Thr 115 120 125 Val Gly Glu Lys Val Phe Ser Ser Asn Gly Gln Ser Ile Thr Phe Asp 130 135 140 Ala Ile Gln Glu Ala Cys Ala Arg Ala Gly Gly Arg Ile Ala Val Pro 145 150 155 160 Arg Asn Pro Glu Glu Asn Glu Ala Ile Ala Ser Phe Val Lys Lys Tyr 165 170 175 Asn Thr Tyr Ala Tyr Val Gly Leu Thr Glu Gly Pro Ser Pro Gly Asp 180 185 190 Phe Arg Tyr Ser Asp Gly Thr Pro Val Asn Tyr Thr Asn Trp Tyr Arg 195 200 205 Gly Glu Pro Ala Gly Arg Gly Lys Glu Lys Cys Val Glu Met Tyr Thr 210 215 220 Asp Gly Gln Trp Asn Asp Arg Asn Cys Leu Tyr Ser Arg Leu Thr Ile 225 230 235 240 Cys Glu Phe 97 681 DNA Homo sapiens CDS (81)..(578) 97 ccaagcacct ggaggctctg tgtgtgggtc gctgatttct tggagcctga aaagaaggag 60 cagcgactgg acccagagcc atg tgg ctg tgc cct ctg gcc ctc acc ctc atc 113 Met Trp Leu Cys Pro Leu Ala Leu Thr Leu Ile 1 5 10 ttg atg gca gcc tct ggt gct gcg tgc gaa gtg aag gag ctc caa gcc 161 Leu Met Ala Ala Ser Gly Ala Ala Cys Glu Val Lys Glu Leu Gln Ala 15 20 25 aca ctc cac gac ttc aga cat caa atc ctg cag aca agg gga gcc ctc 209 Thr Leu His Asp Phe Arg His Gln Ile Leu Gln Thr Arg Gly Ala Leu 30 35 40 agt ctg cag ggc tcc ata atg aca gta gga gag aag gtc ttc tct agc 257 Ser Leu Gln Gly Ser Ile Met Thr Val Gly Glu Lys Val Phe Ser Ser 45 50 55 aat ggg cag tcc atc act ttt gat gcc att cag gag gca tgt gcc aga 305 Asn Gly Gln Ser Ile Thr Phe Asp Ala Ile Gln Glu Ala Cys Ala Arg 60 65 70 75 gca ggc ggc cgc att gct gtc cca agg aat cca gag gaa aat gag gcc 353 Ala Gly Gly Arg Ile Ala Val Pro Arg Asn Pro Glu Glu Asn Glu Ala 80 85 90 att gca agc ttc gtg aag aag tac aac aca tat gcc tat gta ggc ctg 401 Ile Ala Ser Phe Val Lys Lys Tyr Asn Thr Tyr Ala Tyr Val Gly Leu 95 100 105 act gag ggt ccc agc cct gga gac ttc cgc tac tca gat ggg acc cct 449 Thr Glu Gly Pro Ser Pro Gly Asp Phe Arg Tyr Ser Asp Gly Thr Pro 110 115 120 gta aac tac acc aac tgg tac cga ggg gag cct gca ggt cgg gga aaa 497 Val Asn Tyr Thr Asn Trp Tyr Arg Gly Glu Pro Ala Gly Arg Gly Lys 125 130 135 gag aag tgt gtg gag atg tac aca gat ggg cag tgg aat gac agg aac 545 Glu Lys Cys Val Glu Met Tyr Thr Asp Gly Gln Trp Asn Asp Arg Asn 140 145 150 155 tgc ctg tac tcc cga ctg acc atc tgt gag ttc tgagaggcat ttaggccatg 598 Cys Leu Tyr Ser Arg Leu Thr Ile Cys Glu Phe 160 165 ggacagggag gatcctgtct ggccttcagt ttccatcccc aggatccact tggtctgtga 658 gatgctagaa ctccctttca aca 681 98 166 PRT Homo sapiens 98 Met Trp Leu Cys Pro Leu Ala Leu Thr Leu Ile Leu Met Ala Ala Ser 1 5 10 15 Gly Ala Ala Cys Glu Val Lys Glu Leu Gln Ala Thr Leu His Asp Phe 20 25 30 Arg His Gln Ile Leu Gln Thr Arg Gly Ala Leu Ser Leu Gln Gly Ser 35 40 45 Ile Met Thr Val Gly Glu Lys Val Phe Ser Ser Asn Gly Gln Ser Ile 50 55 60 Thr Phe Asp Ala Ile Gln Glu Ala Cys Ala Arg Ala Gly Gly Arg Ile 65 70 75 80 Ala Val Pro Arg Asn Pro Glu Glu Asn Glu Ala Ile Ala Ser Phe Val 85 90 95 Lys Lys Tyr Asn Thr Tyr Ala Tyr Val Gly Leu Thr Glu Gly Pro Ser 100 105 110 Pro Gly Asp Phe Arg Tyr Ser Asp Gly Thr Pro Val Asn Tyr Thr Asn 115 120 125 Trp Tyr Arg Gly Glu Pro Ala Gly Arg Gly Lys Glu Lys Cys Val Glu 130 135 140 Met Tyr Thr Asp Gly Gln Trp Asn Asp Arg Asn Cys Leu Tyr Ser Arg 145 150 155 160 Leu Thr Ile Cys Glu Phe 165 99 1161 DNA Homo sapiens CDS (174)..(917) 99 ggctctttct agctataaac actgcttgcc gcgctgcact ccaccacgcc tcctccaagt 60 cccagcgaac ccgcgtgcaa cctgtcccga ctctagccgc ctcttcagct cacggatcaa 120 ttcccaagtc gctggaggct ctgtgtgtgg gagcagcgac tggacccaga gcc atg 176 Met 1 tgg ctg tgc cct ctg gcc ctc aac ctc atc ttg atg gca gcc tct ggt 224 Trp Leu Cys Pro Leu Ala Leu Asn Leu Ile Leu Met Ala Ala Ser Gly 5 10 15 gct gtg tgc gaa gtg aag gac gtt tgt gtt gga agc cct ggt atc ccc 272 Ala Val Cys Glu Val Lys Asp Val Cys Val Gly Ser Pro Gly Ile Pro 20 25 30 ggc act cct gga tcc cac ggc ctg cca ggc agg gac ggg aga gat ggt 320 Gly Thr Pro Gly Ser His Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly 35 40 45 gtc aaa gga gac cct ggc cct cca ggc ccc atg ggt cca cct gga gaa 368 Val Lys Gly Asp Pro Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Glu 50 55 60 65 atg cca tgt cct cct gga aat gat ggg ctg cct gga gcc cct ggt atc 416 Met Pro Cys Pro Pro Gly Asn Asp Gly Leu Pro Gly Ala Pro Gly Ile 70 75 80 cct gga gag tgt gga gag aag ggg gag cct ggc gag agg ggc cct cca 464 Pro Gly Glu Cys Gly Glu Lys Gly Glu Pro Gly Glu Arg Gly Pro Pro 85 90 95 ggg ctt cca gct cat cta gat gag gag ctc caa gcc aca ctc cac gac 512 Gly Leu Pro Ala His Leu Asp Glu Glu Leu Gln Ala Thr Leu His Asp 100 105 110 ttt aga cat caa atc ctg cag aca agg gga gcc ctc agt ctg cag ggc 560 Phe Arg His Gln Ile Leu Gln Thr Arg Gly Ala Leu Ser Leu Gln Gly 115 120 125 tcc ata atg aca gta gga gag aag gtc ttc tcc agc aat ggg cag tcc 608 Ser Ile Met Thr Val Gly Glu Lys Val Phe Ser Ser Asn Gly Gln Ser 130 135 140 145 atc act ttt gat gcc att cag gag gca tgt gcc aga gca ggc ggc cgc 656 Ile Thr Phe Asp Ala Ile Gln Glu Ala Cys Ala Arg Ala Gly Gly Arg 150 155 160 att gct gtc cca agg aat cca gag gaa aat gag gcc att gca agc ttc 704 Ile Ala Val Pro Arg Asn Pro Glu Glu Asn Glu Ala Ile Ala Ser Phe 165 170 175 gtg aag aag tac aac aca tat gcc tat gta ggc ctg act gag ggt ccc 752 Val Lys Lys Tyr Asn Thr Tyr Ala Tyr Val Gly Leu Thr Glu Gly Pro 180 185 190 agc cct gga gac ttc cgc tac tca gac ggg acc cct gta aac tac acc 800 Ser Pro Gly Asp Phe Arg Tyr Ser Asp Gly Thr Pro Val Asn Tyr Thr 195 200 205 aac tgg tac cga ggg gag ccc gca ggt cgg gga aaa gag cag tgt gtg 848 Asn Trp Tyr Arg Gly Glu Pro Ala Gly Arg Gly Lys Glu Gln Cys Val 210 215 220 225 gag atg tac aca gat ggg cag tgg aat gac agg aac tgc ctg tac tcc 896 Glu Met Tyr Thr Asp Gly Gln Trp Asn Asp Arg Asn Cys Leu Tyr Ser 230 235 240 cga ctg acc atc tgt gag ttc tgagaggcat ttaggccatg ggacagggag 947 Arg Leu Thr Ile Cys Glu Phe 245 gacgctctct ggcctccatc ctgaggctcc acttggtctg tgagatgcta gaactccctt 1007 caacagaatt gatccctgct gcccgtgctg gagagcttca aggtcagctt cctgagcgct 1067 ctctcgagga gtacactaag aagctcaaca cccagtgagg cgcccgccgc cgcccccctt 1127 cccggtgctc agaataaacg tttccaaagt ggga 1161 100 248 PRT Homo sapiens 100 Met Trp Leu Cys Pro Leu Ala Leu Asn Leu Ile Leu Met Ala Ala Ser 1 5 10 15 Gly Ala Val Cys Glu Val Lys Asp Val Cys Val Gly Ser Pro Gly Ile 20 25 30 Pro Gly Thr Pro Gly Ser His Gly Leu Pro Gly Arg Asp Gly Arg Asp 35 40 45 Gly Val Lys Gly Asp Pro Gly Pro Pro Gly Pro Met Gly Pro Pro Gly 50 55 60 Glu Met Pro Cys Pro Pro Gly Asn Asp Gly Leu Pro Gly Ala Pro Gly 65 70 75 80 Ile Pro Gly Glu Cys Gly Glu Lys Gly Glu Pro Gly Glu Arg Gly Pro 85 90 95 Pro Gly Leu Pro Ala His Leu Asp Glu Glu Leu Gln Ala Thr Leu His 100 105 110 Asp Phe Arg His Gln Ile Leu Gln Thr Arg Gly Ala Leu Ser Leu Gln 115 120 125 Gly Ser Ile Met Thr Val Gly Glu Lys Val Phe Ser Ser Asn Gly Gln 130 135 140 Ser Ile Thr Phe Asp Ala Ile Gln Glu Ala Cys Ala Arg Ala Gly Gly 145 150 155 160 Arg Ile Ala Val Pro Arg Asn Pro Glu Glu Asn Glu Ala Ile Ala Ser 165 170 175 Phe Val Lys Lys Tyr Asn Thr Tyr Ala Tyr Val Gly Leu Thr Glu Gly 180 185 190 Pro Ser Pro Gly Asp Phe Arg Tyr Ser Asp Gly Thr Pro Val Asn Tyr 195 200 205 Thr Asn Trp Tyr Arg Gly Glu Pro Ala Gly Arg Gly Lys Glu Gln Cys 210 215 220 Val Glu Met Tyr Thr Asp Gly Gln Trp Asn Asp Arg Asn Cys Leu Tyr 225 230 235 240 Ser Arg Leu Thr Ile Cys Glu Phe 245 101 349 DNA Homo sapiens CDS (19)..(294) 101 ggtgagacaa ggaagagg atg tct gag ctg gag aag gcc atg gtg gcc ctc 51 Met Ser Glu Leu Glu Lys Ala Met Val Ala Leu 1 5 10 atc gac gtt ttc cac caa tat tct gga agg gag gga gac aag cac aag 99 Ile Asp Val Phe His Gln Tyr Ser Gly Arg Glu Gly Asp Lys His Lys 15 20 25 ctg aag aaa tcc gaa ctc aag gag ctc atc aac aat gag ctt tcc cat 147 Leu Lys Lys Ser Glu Leu Lys Glu Leu Ile Asn Asn Glu Leu Ser His 30 35 40 ttc tta gag gaa atc aaa gag cag gag gtt gtg gac aaa gtc atg gaa 195 Phe Leu Glu Glu Ile Lys Glu Gln Glu Val Val Asp Lys Val Met Glu 45 50 55 aca ctg gac aat gat gga gac ggc gaa tgt gac ttc cag gaa ttc atg 243 Thr Leu Asp Asn Asp Gly Asp Gly Glu Cys Asp Phe Gln Glu Phe Met 60 65 70 75 gcc ttt gtt gcc atg gtt act act gcc cgc cac gag ttc ttt gaa cat 291 Ala Phe Val Ala Met Val Thr Thr Ala Arg His Glu Phe Phe Glu His 80 85 90 gag tgagattaga aagcagccaa acctttcctg taacagagac ggtcatgcaa gaaag 349 Glu 102 92 PRT Homo sapiens 102 Met Ser Glu Leu Glu Lys Ala Met Val Ala Leu Ile Asp Val Phe His 1 5 10 15 Gln Tyr Ser Gly Arg Glu Gly Asp Lys His Lys Leu Lys Lys Ser Glu 20 25 30 Leu Lys Glu Leu Ile Asn Asn Glu Leu Ser His Phe Leu Glu Glu Ile 35 40 45 Lys Glu Gln Glu Val Val Asp Lys Val Met Glu Thr Leu Asp Asn Asp 50 55 60 Gly Asp Gly Glu Cys Asp Phe Gln Glu Phe Met Ala Phe Val Ala Met 65 70 75 80 Val Thr Thr Ala Arg His Glu Phe Phe Glu His Glu 85 90 103 271 DNA Homo sapiens CDS (19)..(216) 103 ggtgagacaa ggaagagg atg tct gag ctg gag aag gcc atg gtg gcc ctc 51 Met Ser Glu Leu Glu Lys Ala Met Val Ala Leu 1 5 10 atc gac gtt ttc cac caa tat tct gga agg gag gga gac aag cac aag 99 Ile Asp Val Phe His Gln Tyr Ser Gly Arg Glu Gly Asp Lys His Lys 15 20 25 ctg aag aaa tcc gaa ctc aag gag ctc atc aac aat gag ctt tcc cat 147 Leu Lys Lys Ser Glu Leu Lys Glu Leu Ile Asn Asn Glu Leu Ser His 30 35 40 ttc tta gag gaa atc aaa gag cag gag gtt gtg gtt act act gcc tgc 195 Phe Leu Glu Glu Ile Lys Glu Gln Glu Val Val Val Thr Thr Ala Cys 45 50 55 cac gag ttc ttt gaa cat gag tgagattaga aagcagccaa acctttcctg 246 His Glu Phe Phe Glu His Glu 60 65 taacagagac ggtcatgcaa gaaag 271 104 66 PRT Homo sapiens 104 Met Ser Glu Leu Glu Lys Ala Met Val Ala Leu Ile Asp Val Phe His 1 5 10 15 Gln Tyr Ser Gly Arg Glu Gly Asp Lys His Lys Leu Lys Lys Ser Glu 20 25 30 Leu Lys Glu Leu Ile Asn Asn Glu Leu Ser His Phe Leu Glu Glu Ile 35 40 45 Lys Glu Gln Glu Val Val Val Thr Thr Ala Cys His Glu Phe Phe Glu 50 55 60 His Glu 65 105 19 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 105 atcttgcctg cttcagcaa 19 106 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 106 tcaaatcctg atccagctgt gtctcg 26 107 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 107 ggatggcaga catattcatg ac 22 108 17 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 108 ggccatcttg cctgctt 17 109 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 109 tatcctgatc cagctgtgtc tcgtgt 26 110 24 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 110 ctccctctca tactgcatat tcat 24 111 19 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 111 gtccactcag ctggagctg 19 112 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 112 taacttggac tcccaggacc tcctga 26 113 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 113 cagctggatc aggatttgag 20 114 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 114 caagggcatc accaatttga 20 115 24 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 115 taggatgtcc agctgcccgt catc 24 116 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 116 gcccactcca ggtacaaagt tc 22 117 24 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 117 ttctttggac agattactga gctt 24 118 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 118 ttcctcatcg attggcaact tcaatg 26 119 21 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 119 tcttcgagat agctggtgat g 21 120 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 120 gatgtgaaag tcaccaggaa tct 23 121 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 121 tttaccatag cgtgtccaat gcctga 26 122 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 122 gatattgtca ccgaacaatg tagttt 26 123 19 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 123 gcaccacatc caccatttc 19 124 24 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 124 tcagcagcaa gcatcattca gtgc 24 125 19 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 125 gatgccggtg acctgtaga 19 126 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 126 gagacaagtc ctaaatgccg ac 22 127 34 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 127 taacaatctt ttgttggatt gaaacagcta atcc 34 128 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 128 ctagtagtgc cagcctgaca aa 22 129 21 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 129 aaaatttcag gcacaccaaa g 21 130 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 130 taattgaact gcagaactgc ttcctg 26 131 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 131 tctcctttca tgtgaacgtc tt 22 132 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 132 caagagagaa aaggctgctt tg 22 133 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 133 tggaggagtc ccctacgcct ccc 23 134 19 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 134 cacagccgca gaataaggc 19 135 21 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 135 gtgaacagca gagctgaaat g 21 136 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 136 tcccgtgcca accctggggg aca 23 137 17 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 137 ggggactcct cccagac 17 138 21 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 138 gcatcagtgg aatgttcgtt t 21 139 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 139 tcagccaggc cactccaagc aca 23 140 19 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 140 caccgctgag aaaccaaac 19 141 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 141 gcgattcttg agcaacactt 20 142 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 142 tcacctcgct cagcaaggca tgg 23 143 25 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 143 ccatagatga catactgcat cagtt 25 144 29 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 144 gagctacctt ataaagacca tctgtacat 29 145 29 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 145 tccactgtga aatggagttt caaaatcac 29 146 28 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 146 atatgtgctc ctagtcttat gttcatgt 28 147 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 147 actctctgac ccagctcttc tc 22 148 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 148 tccactccta cggccgcctg tat 23 149 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 149 gagaacaggc cattgaatat ga 22 150 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 150 actctctgac ccagctcttc tc 22 151 23 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 151 tccactccta cggccgcctg tat 23 152 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 152 gagaacaggc cattgaatat ga 22 153 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 153 actccaccaa gaagatccag tt 22 154 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 154 ttctcttctg gaagctctgc gacttc 26 155 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 155 gcacgaagaa gaggaatttc tt 22 156 15 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 156 ccaccaagac gcagc 15 157 21 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 157 taagccaccg atgatgccta t 21 158 18 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 158 gagcaggtgg ttgtaggg 18 159 17 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 159 gcgtgcgaag tgaagga 17 160 26 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 160 tctccaagcc acactccacg acttca 26 161 18 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 161 ctgagggctc cccttgtc 18 162 16 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 162 tggccctcat cgacgt 16 163 27 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 163 tagctcatca acaatgagct ttcccat 27 164 22 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 164 gcagtagtaa ccacaacctc ct 22 165 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 165 atgtccgcgc tgcgacctct 20 166 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 166 atgtccgcgc tgcgacctct 20 167 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 167 cgggagcgag gcaaaggtca 20 168 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 168 aacgaccgcc gcaggcacca 20 169 20 DNA Artificial Sequence Description of Artifical Sequence Primer/Probe 169 gcttggacct cgataacggg 20 

What is claimed is:
 1. An isolated polypeptide comprising the mature form of an amino acid sequenced selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 52. 2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 52. 3. An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 52. 4. An isolated polypeptide, wherein the polypeptide comprises an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 52. 5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring.
 6. A composition comprising the polypeptide of claim 1 and a carrier.
 7. A kit comprising, in one or more containers, the composition of claim
 6. 8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim
 1. 9. A method for determining the presence or amount of the polypeptide of claim 1 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to an antibody that binds immunospecifically to the polypeptide; and (c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample.
 10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and b) comparing the expression of said polypeptide in the sample of step (a) to the expression of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the level of expression of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.
 11. A method of identifying an agent that binds to the polypeptide of claim 1, the method comprising: (a) introducing said polypeptide to said agent; and (b) determining whether said agent binds to said polypeptide.
 12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector.
 13. A method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of the polypeptide of claim 1, the method comprising: (a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide; (b) contacting the cell with a composition comprising a candidate substance; and (c) determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition in the absence of the substance, the substance is identified as a potential therapeutic agent.
 14. A method for screening for a modulator of activity of or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising: (a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1; (b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and (c) comparing the activity of said polypeptide in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator activity of or latency or predisposition to, a pathology associated with the polypeptide of claim
 1. 15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.
 16. A method for modulating the activity of the polypeptide of claim 1, the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.
 17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject.
 18. The method of claim 17, wherein the subject is a human.
 19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 52 or a biologically active fragment thereof.
 20. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and
 52. 21. The nucleic acid molecule of claim 20, wherein the nucleic acid molecule is naturally occurring.
 22. A nucleic acid molecule, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and
 52. 23. An isolated nucleic acid molecule encoding the mature form of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
 52. 24. An isolated nucleic acid molecule comprising a nucleic acid selected from the group consisting of 2n−1, wherein n is an integer between 1 and
 52. 25. The nucleic acid molecule of claim 20, wherein said nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 52, or a complement of said nucleotide sequence.
 26. A vector comprising the nucleic acid molecule of claim
 20. 27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule.
 28. A cell comprising the vector of claim
 26. 29. An antibody that immunospecifically binds to the polypeptide of claim
 1. 30. The antibody of claim 29, wherein the antibody is a monoclonal antibody.
 31. The antibody of claim 29, wherein the antibody is a humanized antibody.
 32. A method for determining the presence or amount of the nucleic acid molecule of claim 20 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to a probe that binds to said nucleic acid molecule; and (c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in said sample.
 33. The method of claim 32 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.
 34. The method of claim 33 wherein the cell or tissue type is cancerous.
 35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression of the nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of expression of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
 36. A method of producing the polypeptide of claim 1, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and
 52. 37. The method of claim 36 wherein the cell is a bacterial cell.
 38. The method of claim 36 wherein the cell is an insect cell.
 39. The method of claim 36 wherein the cell is a yeast cell.
 40. The method of claim 36 wherein the cell is a mammalian cell.
 41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and
 52. 42. The method of claim 41 wherein the cell is a bacterial cell.
 43. The method of claim 41 wherein the cell is an insect cell.
 44. The method of claim 41 wherein the cell is a yeast cell.
 45. The method of claim 41 wherein the cell is a mammalian cell. 